ArchiveAdvanced Search

Similar Papers

Print this page Create this page as PDF Introduce this page to your friend Blind help
Volume 6, 2017, Issue 12, Pages 240-247; Paper doi: 10.15412/J.JBTW.01061201; Paper ID: 16521.
CrossMark
Previous PaperPrevious Paper      Next PaperNext Paper


Long Non-coding RNAs Expression in Renal Cell Carcinoma
(Review)
  • 1 Urogenital Stem Cell Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  • 2 Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  • Correspondence should be addressed to Soudeh Ghafouri-Fard, Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Tel: ; Fax: ; Email: s.ghafourifard@sbmu.ac.ir1.

Abstract

Renal cell carcinoma (RCC) is among common cancers of the urogenital system. Several cancer-related pathways have been shown to be implicated in its pathogenesis. More recently, dysregulation of a group of non-coding RNAs named long non-coding RNAs (lncRNAs) have been demonstrated in many cancer types such as RCC. LncRNAs have been classified to oncogenic and tumor suppressor lncRNAs based on the pattern of expression in RCC samples as well as functional in vitro studies. Expression of several oncogenic lncRNAs such as CCAT2, HOTAIR, UCA1, TUG1 and FTX in RCC samples has been shown to be associated with tumor size and tumor stage. In addition, expression levels of numerous lncRNAs have been demonstrated to be independent prognostic factors in RCC patients. Consequently, lncRNA signature would be applied as diagnostic or prognostic biomarker as well as target for treatment modalities.

Keywords

lncRNA, Renal cell carcinoma, Biomarker

1. INTRODUCTION
R

enal cell carcinoma (RCC) is among malignancies whose frequency has an increasing trend in developing countries. The same as other cancers, early diagnosis is associated with better patient outcome and possibility of application of curative treatments (1). This malignancy has been recognized to have extensive heterogeneity and a genetically complex background. Several cancer-related pathways such as von Hippel-Lindau/ Hypoxia-inducible factor (VHL/HIF) pathway, chromatin remodeling/histone methylation pathway and Phosphatidylinositol-3-Kinase and Protein Kinase B (PI3K/AKT) pathway have been implicated in the pathogenesis of RCC (2, 2). Clear cell renal cell carcinoma (ccRCC) is the most frequent type of this malignancy with both sporadic and familial forms in which VHL gene mutations play causative roles (2, 3). In spite of extensive efforts to find appropriate biomarkers for this malignancy, no ideal diagnostic or prognostic biomarker has been identified until recently (3, 4). However, recent studies have introduced serum tissue factor (4) and blood expression level of Chemokine (C-X-C motif) ligand 7 (CXCL7) (5) as diagnostic biomarkers for RCC while C-reactive protein (6) as a prognostic biomarker for this malignancy. More recently, Yen et al. have introduced a reversed phase liquid chromatographic method for simultaneous measurement of creatinine, quinolinic acid, gentisic acid and 4-hydroxybenzoic acid in urine as biomarkers for RCC. However, their method has a number of limitations due the presence of background from the urine matrix or other reagents (7). In addition, a recent publication has assessed the presence of frequently mutated genes in circulating tumor DNA (ctDNA) of RCC patients using whole-exome sequencing of ctDNA. Such somatic mutations were detected in two third of RCC patients but only two of the control patients (8). Besides, the possibility of application of myeloid cell biomarkers for the differential diagnosis, prognosis, and monitoring of RCC has been assessed (9). Another study has introduced a panel of 21 volatile organic compounds (VOCs) with the ability to differentiate RCC patients from controls. The capability of two of them for such purpose was confirmed in further studies (2-oxopropanal and 2,5,8-trimethyl-1,2,3,4-tetrahydronaphthalene-1-ol). Consequently, they have demonstrated the significance of urinary volatilome for RCC diagnosis (10, 11). Researchers have focused on assessment of genetic and epigenetic changes during the course of RCC development to unveil the underlying causes of this malignancy and introduce novel biomarkers for it. Long non-coding RNAs (lncRNAs) comprise a large fraction of non-protein coding transcripts of human genome with sizes larger than 200 nucleotides. They control gene expression at epigenetic, transcriptional and post-transcriptional levels (11). Such vast domain of gene expression regulation has led to participation of lncRNAs in several cancer-related pathways (12, 15). Expression analyses have provided several clues indicating dysregulation of lncRNAs in malignancies (15, 20). In addition, numerous single nucleotide polymorphisms (SNPs) within lncRNA coding regions or regulatory sequences have been shown to modulate cancer risk in different populations (20). LncRNAs exert tissue specific roles during tumorigenesis. Based on these roles they are classified to oncogenic or tumor suppressor lncRNAs. Expression analyses as well as in vitro functional studies have revealed participation of several lncRNAs in RCC. Table 1 presents a summary of lncRNAs implicated in RCC. Considering the high mortality and morbidity rate of RCC and the necessity for finding appropriate biomarkers for early detection of this malignancy, we aimed at evaluation of the role of lncRNAs in RCC to find the underlying genetic cause of this disorder which might facilitate identification of diagnostic or prognostic biomarkers as well as design of specific treatments for this malignancy.

Table 1. Long non-coding RNAs implicated in renal cell carcinoma.

More than a decade before, aHIF has been identified as a natural antisense transcript originated from hypoxia inducible factor 1α (HIF1α) gene sequences and up-regulated in all ccRCC samples examined. Its overexpression in this specific cancer type implied an oncogenic role for it (40, 25). More recently, Colon cancer-associated transcript-1 (CCAT1) expression has been demonstrated to be elevated in RCC tissues and cell lines. Its silencing has decreased cell viability and induced the apoptosis of RCC cells in vitro. Notably, CCAT1 has a physical interaction with the anti-apoptotic protein, Livin. Functional studies have shown that CCAT1 suppresses RCC cell apoptosis and enhances cell viability through enhancing the expression of Livin (25). The effect of CCAT1 on apoptosis has been demonstrated in Figure 1 .

Figure 1. CCAT1 increases LIVIN protein stability and inhibits mitochondrial induced apoptosis

Colon cancer-associated transcript 2 (CCAT2) expression has been shown to be elevated in ccRCC cell lines and tissues as well. CCAT2 silencing resulted in decreased cell proliferation, induction of apoptosis and activation of Wnt/β-catenin signaling pathway in RCC cell lines while its forced overexpression increased oncogenic characteristics of these cells. The effects of CCAT2 knock down in inhibition of RCC tumor cells has been confirmed in mice xenograft model as well (26, 41). Metastatic renal cell carcinoma-associated transcript 1 (MRCCAT1) has been identified through microarray analysis of RCC samples. The expression of this lncRNA has been shown to be elevated in metastatic ccRCC tissues and associated with the metastatic characteristics of ccRCC. Knock-in studies have shown that MRCCAT1 enhances ccRCC cells proliferation, migration, and invasion while its silencing suppresses ccRCC cells proliferation, migration, and invasion in vitro, and ccRCC metastasis in vivo. MRCCAT1 has a role in induction of p38-MAPK signaling pathway through inhibition of NPR3 transcription by recruiting PRC2 to its promoter (41, 27). HOX Transcript Antisense RNA (HOTAIR) has enhanced RCC cell proliferation and growth in vitro and in vivo. HOTAIR exert an inhibitory role on expression of Salvador homolog 1 (SAV1) through increasing histone H3K27 methylation. Consequently, this lncRNA activates Hippo pathway in RCC cells (27). In addition, HOTAIR role in enhancing cancer cell metastasis has been shown to be exerted through reprogramming chromatin organization. Forced expression of HOTAIR has resulted in down-regulation of histone demethylase JMJD3 as well as its target gene Snail, while increased the level of histonemethy transferase EZH2 target gene PCDHB5. So HOTAIR influences both histone metylation and demethylation at various gene loci altering chromatin state in a way that facilitates metastasis program (42, 43). Urothelial carcinoma-associated 1 (UCA1) has also been shown to exert oncogenic roles in RCC. UCA1 up-regulation has been demonstrated in RCC samples and cell lines (43, 28). Its silencing has inhibited RCC proliferation and S-phase cell number in vitro. This lncRNA has been shown to be associated with enhancer of zeste homolog 2, which inhibited p21 expression through epigenetic mechanisms. miR-495 has also been suggested by both bioinformatics tools and functional studies to be a target of UCA1 in RCC (28, 29). Taurine Up-Regulated 1 (TUG1) expression levels have been shown to be elevated in RCC tissues compared with adjacent normal tissues (29). TUG1 silencing has inhibited RCC cells migration, invasion and proliferation while has induced apoptosis (44, 30). Similarly, expression level of the lncRNA five prime to Xist (FTX) has been higher in RCC tissues compared with normal tissues. Its silencing in RCC cells suppressed cell proliferation rate, colony formation ability, cell cycle progression as well as cell migration and invasion  (30). Long non-coding ribonucleic acid activated by transforming growth factor β (lncRNA-ATB) silencing has resulted in suppression of cell proliferation, epithelial-to-mesenchymal transition (EMT) program, cell migration and invasion while has induced apoptosis (45, 46).  LncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT-1) has also been implicated in RCC pathogenesis. Its knock-down has resulted in induction of cell apoptosis and reduction of RCC cell viability. MALAT-1 has been shown to increase the stability of the anti-apoptotic protein Livin (46, 47). Another study has shown that MALAT-1 transcription is induced by c-Fos. It has also been demonstrated to interact with Ezh2. MALAT-1 knock-down has also resulted in induction of E-cadherin expression and reduction of β-catenin expression through Ezh2 (47, 33). In addition, MALAT-1 has been regarded as a competing endogenous RNA (ceRNA) which impedes miR-200s and increases ZEB2 expression in ccRCC (33, 48). Figure 2 shows the mechanisms of oncogenic roles of MALAT-1 in RCC. RCCRT1 elevated expression has also been detected in RCC, especially in high-grade RCC tissues. Besides, its silencing has inhibited migration and invasion in RCC cell lines (48, 37). Knockdown of SPRY4-IT1 has similar effect in RCC cells (37).

Figure 2. MALAT-1 induces expression of EZH-2 and β-catenin. β-catenin increases expression of C-myc and cyclin-D1 resulting in cell cycle progression (A). MALAT-1 cooperates with EZH2 produces PRC complex to inhibit expression of E-cadherin and promote metastasis (B)

The expression of the lncRNA differentiation antagonizing nonprotein coding RNA (DANCR) has been shown to be decreased in RCC tissues compared with adjacent normal tissues. Forced overexpression of this lncRNA has inhibited RCC cell proliferation, migration and invasion, and triggered apoptosis in these cells. So this lncRNA has been suggested as a tumor suppressor gene and a potential biomarker in RCC (24). Serum deprivation response antisense (SDPR-AS) in has been shown to be down-regulated in RCC tissues compared to the matched normal tissues. Overexpression of this lncRNA in RCC cells inhibited cell migration and invasion, but not cell growth (49). BX357664 is another tumor suppressor gene in RCC whose forced overexpression has decreased migration, invasion, and proliferation of RCC cells. Such anti-tumorigenic roles are exerted through inhibition of the TGF-β1/p38/HSP27 pathway (32). The paternally imprinted non-coding MEG3 has been also regarded as a tumor suppressor in RCC because it has been shown to be down-regulated in primary RCC tissues due to epigenetic silencing throughout the 14q32 gene cluster (50, 35). Knock-in studies have shown the effect of MEG3 on decreasing the viability and induction of apoptosis in RCC cells. Besides, overexpression of MEG3 has resulted in inhibition of Bcl-2 and procaspase-9 proteins expression while increased the expression of cleaved caspase-9 protein, and enhanced the release of cytochrome c protein to cytoplasm. So MEG3 triggers the apoptosis of RCC cells probably through activating the mitochondrial pathway (35, 36). LncRNA neuroblastoma associated transcript-1 (NBAT-1) expression has been remarkably down-regulated in ccRCC tissues and renal cancer cells compared with neighboring normal tissues and normal human proximal tubule epithelial cell line. In addition, its silencing has increased renal cancer cell proliferation, migration and invasion (36, 51). Figure 3 shows the inhibitory effect of NBAT-1 on metastasis and angiogenesis. Growth arrest-specific transcript 5 (GAS5) overexpression in RCC has suppressed cell proliferation, migration and invasion, triggered cell apoptosis and arrested cell cycling. Consequently, GAS5 has been suggested as a tumor suppressor for RCC (51).

Figure 3. NBAT-1 acts as tumor suppressor gene by inhibiting EZH2 expression. EZH2 inhibits E-cadherin and induces VEGF and cyclin D expression leading to angiogenesis and metastasis

TRIM52 antisense RNA 1 (TRIM52AS1) is another tumor suppressor lncRNA which has been down-regulated in RCC. The overexpression of TRIM52AS1 has inhibited cell migration and proliferation while induced apoptosis of the RCC cells (34, 39). CADM1-AS1 expression has also been demonstrated to be decreased in ccRCC tissues in compared with adjacent non-tumor tissues. Its silencing has increased growth and migration while decreased apoptosis of RCC cells (39).

Sorafenib resistance-associated lncRNA (SRLR) expression has been shown to be increased in intrinsically sorafenib-resistant RCCs. In vitro studies have confirmed the role of this lncRNA in induction of sorafenib resistance in RCC cells. The role of SRLR in induction of drug resistance is exerted through its binding to NF-κB and subsequent elevation of IL-6 transcription, resulting in the activation of STAT3. Clinical data has also shown the association between SRLR expression and poor responses to sorafenib in RCC patients (31).

Expression of several oncogenic lncRNAs such as CCAT2, HOTAIR, UCA1, TUG1 and FTX in RCC samples has been shown to be associated with tumor size and tumor stage (26, 26). CCAT2, MRCCAT1, HOTAIR, UCA1, TUG1 and MALAT-1 expression levels have been shown to be markers of overall survival in RCC patients (26, 27). In addition, elevated expression of HOTAIR has been regarded as marker for poor prognosis of RCC after surgery (27). Besides, expression levels of lncRNA-ATB and RCCRT1 have been associated with tumor stages, histological grade, vascular invasion, lymph node metastasis and distant metastasis in RCC patients (45, 48). Elevated levels of SPRY4-IT1 and H19 expressions have been associated with advanced clinical stage and poorer prognosis ccRCC patients (37, 53). In addition, multivariate analyses by Cox's proportional hazard model and Kaplan-Meier analysis demonstrated SPRY4-IT1 and H19 expression levels as independent prognostic factors in ccRCC, respectively (37, 53). On the other hand, higher expressions of SDPR-AS, NBAT-1 and CADM1-AS1 have been shown to be associated with better overall survival (36, 39). 

Several oncogenic lncRNAs have been shown to participate in RCC development and progression. In addition, lots of them have been suggested as prognostic markers and putative targets for development of novel treatment options. For some lncRNAs such as MALAT-1 the prognostic implication in RCC patients have been supported by meta-analysis of data available in the literature (54, 2). Furthermore, the high rate of mutations detected in chromatin modifier genes in ccRCC indicates the importance of nucleosome dynamics model in its pathogenesis (2, 12). Considering the crucial role of lncRNAs in regulation of histone modifications as well as epigenetic alterations (12), lncRNAs are anticipated to participate in RCC pathogenesis as well. In addition, several lncRNAs have been shown to modulate expression of genes implicated in cancer related pathways such as VHL/HIF, PI3K/AKT and mTOR pathways which implies their role in RCC pathogenesis. Some other lncRNAs participate in process which supports their role in metastasis. Among lncRNAs with putative role in RCC, MALAT-1 function in RCC pathogenesis has been elucidated. Its expression is induced by c-Fos downstream of the VHL pathway and it interacts with Polycomb protein EZH2 to trigger EMT (50, 55). Such data has been provided by functional studies in RCC cell lines. More recently, the advent of high throughput technologies such as next generation sequencing has facilitated assessment of lncRNA expression in all cancer types such as RCC. For instance, integrative analysis of RNA-sequencing profiles of primary ccRCC samples has shown association of certain lncRNA subclasses with clinicopathological and genomic characteristics of RCC (55). Such studies would facilitate lncRNA classification with the aim of recognizing tumor course and patients' outcome.

The results of in vitro studies as well as the limited data obtained from in vivo studies have provided the hope for direct targeting of oncogenic lncRNAs as a therapeutic modality for cancer. The most applied method up to now has been antisense technologies. Catalytic nucleic acids (CNAs) such as ribozymes and DNAzymes have also been suggested as tools for down-regulation of lncRNAs (50, 50). In addition, inhibition of lncRNA interactions with their protein partners has been proposed as an alternative strategy (50). Future studies are needed to evaluate the effects of these modalities in cell lines experiments as well as animal models.

4. CONCLUSION

In conclusion, lncRNAs have been shown to be implicated in the pathogenesis of RCC in a way similar to other malignancies. This potentiates them as targets of new treatment modalities. In addition, they exert regulatory roles in well-defined pathways RCC tumorigenesis which makes them appropriate biomarkers for this malignancy.

ACKNOWLEDGMENT

Not mentioned any acknowledgment by authors.

Not mentioned any Funding/Support by authors.

AUTHORS CONTRIBUTION

Mohammad Taheri contributed in electronic search and designed figures and table. Mir Davood Omrani and Soudeh Ghafouri-Fard designed the research and supervised it. Soudeh Ghafouri-Fard wrote the manuscript.

CONFLICT OF INTEREST

The authors declared no potential conflicts of interests with respect to the authorship and/or publication of this paper.

REFERENCES

1. Ghafouri-Fard S, Faramarzi S. Renal Cell Carcinoma: a cancer-testis antigen poor malignancy. Asian Pacific Journal of Cancer Biology. 2017;2(3):59-62. [View at Google Scholar].

2. Comprehensive molecular characterization of clear cell renal cell carcinoma. Nature. 2013;499(7456):43-9. [View at Google Scholar]; [View at PubMed].

3. Li M, Wang Y, Cheng L, Niu WT, Zhao GA, Raju JK, et al. Long non-coding RNAs in renal cell carcinoma: A systematic review and clinical implications. Oncotarget. 2017;8(29):48424-35. [View at Google Scholar]; [View at PubMed].

4. Silva D, da Costa BP, Noronha JAP, Carvalhal G. MP39-16 SERUM TISSUE FACTOR AS A BIOMARKER FOR RENAL CLEAR CELL CARCINOMA. The Journal of Urology. 2017;197(4):e499-e500. [View at Publisher]; [View at Google Scholar].

5. Kinouchi T, Uemura M, Wang C, Ishizuya Y, Yamamoto Y, Hayashi T, et al. The expression level of CXCL7 in peripheral blood cells is a potential biomarker for the diagnosis of renal cell carcinoma. Cancer Science. 2017. [View at Google Scholar].

6. Nakayama T, Saito K, Waseda Y, Tanaka H, Inoue M, Ito M, et al. MP39-12 HIGHER SERUM C-REACTIVE PROTEIN LEVEL REPRESENTS THE IMMUNOSUPPRESSIVE TUMOR MICROENVIRONMENT IN PATIENTS WITH CLEAR CELL RENAL CELL CARCINOMA. The Journal of Urology. 2017;197(4):e497-e8. [View at Publisher]; [View at Google Scholar].

7. Yen T-A, Dahal KS, Lavine B, Hassan Z, Gamagedara S. Development and validation of high performance liquid chromatographic method for determination of gentisic acid and related Renal Cell Carcinoma biomarkers in urine. Microchemical Journal. 2018;137:85-9. [View at Publisher]; [View at Google Scholar]; [View at PubMed]; [View at Scopus].

8. Laganosky D, Lorentz C, Al-Qassab U, Ogan K, Master VA, Issa M, et al. Use of liquid biopsy for detection of renal cell carcinoma. American Society of Clinical Oncology; 2017. [View at Google Scholar].

9. Singh H, Mendrzyk R, Walter S, Bronte V, Mandruzzato S. Use of myeloid cell biomarkers for the diagnosis of cancer. Google Patents; 2017. [View at Google Scholar].

10. Monteiro M, Moreira N, Pinto J, Pires‐Luís AS, Henrique R, Jerónimo C, et al. GC‐MS metabolomics‐based approach for the identification of a potential VOC‐biomarker panel in the urine of renal cell carcinoma patients. Journal of Cellular and Molecular Medicine. 2017. [View at Google Scholar]; [View at PubMed].

11. Cao JN. The functional role of long non-coding RNAs and epigenetics. Biol Proced Online. 2014;16. [View at Google Scholar].

12. Dianatpour A, Ghafouri-Fard S. The Role of Long Non Coding RNAs in the Repair of DNA Double Strand Breaks. International Journal of Molecular and Cellular Medicine (IJMCM). 2017;6(1):1-12. [View at Google Scholar]; [View at PubMed].

13. Nikpayam E, Tasharrofi B, Sarrafzadeh S, Ghafouri-Fard S. The role of long non-coding RNAs in ovarian cancer. Iranian biomedical journal. 2017;21(1):3. [View at Google Scholar].

14. Tasharrofi B, Soudyab M, Nikpayam E, Iranpour M, Mirfakhraie R, Sarrafzadeh S, et al. Comparative expression analysis of hypoxia‐inducible factor‐alpha and its natural occurring antisense in breast cancer tissues and adjacent noncancerous tissues. Cell biochemistry and function. 2016;34(8):572-8. [View at Publisher]; [View at Google Scholar]; [View at PubMed]; [View at Scopus].

15. Nikpayam E, Soudyab M, Tasharrofi B, Sarrafzadeh S, Iranpour M, Geranpayeh L, et al. Expression analysis of long non-coding ATB and its putative target in breast cancer. Breast Disease. 2017(Preprint):1-10. [View at Publisher]; [View at Google Scholar].

16. Sarrafzadeh S, Geranpayeh L, Ghafouri-fard S. Expression Analysis of Long Non-coding PCAT-1. International Journal of Hematology-Oncology and Stem Cell Research. 2017;11(3):185-91. [View at Google Scholar]; [View at PubMed].

17. Sarrafzadeh S, Geranpayeh L, Tasharrofi B, Soudyab M, Nikpayam E, Iranpour M, et al. Expression Study and Clinical Correlations of MYC and CCAT2 in Breast Cancer Patients. Iranian Biomedical Journal. 2017:0-. [View at Google Scholar].

18. Soudyab M, Iranpour M, Ghafouri-Fard S. The Role of Long Non-Coding RNAs in Breast Cancer. Archives of Iranian Medicine (AIM). 2016;19(7). [View at Google Scholar].

19. Iranpour M, Soudyab M, Geranpayeh L, Mirfakhraie R, Azargashb E, Movafagh A, et al. Expression analysis of four long noncoding RNAs in breast cancer. Tumor Biol. 2016;37(3):2933-40. [View at Publisher]; [View at Google Scholar]; [View at Scopus].

20. Taheri M, Habibi M, Noroozi R, Rakhshan A, Sarrafzadeh S, Sayad A, et al. HOTAIR genetic variants are associated with prostate cancer and benign prostate hyperplasia in an Iranian population. Gene. 2017;613:20-4. [View at Publisher]; [View at Google Scholar]; [View at Scopus].

21. Khorshidi HR, Taheri M, Noroozi R, Sayad A, Ghafouri-Fard S. ANRIL genetic variants in Iranian breast cancer patients. Cell Journal (Yakhteh). 2017;19(Suppl 1):72. [View at Google Scholar]; [View at PubMed].

22. Khorshidi HR, Taheri M, Noroozi R, Soudyab M, Sayad A, et al. Investigation of the Association of HOTAIR Single Nucleotide Polymorphisms and Risk of Breast Cancer in an Iranian Population. International Journal of Cancer Management. 2017; 10(5):e7498. [View at Google Scholar].

23. Taheri M, Pouresmaeili F, Omrani MD, Habibi M, Sarrafzadeh S, Noroozi R, et al. Association of ANRIL gene polymorphisms with prostate cancer and benign prostatic hyperplasia in an Iranian population. Biomarkers in Medicine. 2017;11(5):413-22. [View at Publisher]; [View at Google Scholar]; [View at Scopus].

24. Jin L, Fu H, Quan J, Pan X, He T, Hu J, et al. Overexpression of long non-coding RNA differentiation antagonizing non-protein coding RNA inhibits the proliferation, migration and invasion and promotes apoptosis of renal cell carcinoma. Mol Med Rep. 2017. [View at Google Scholar]; [View at PubMed].

25. Chen S, Ma P, Li B, Zhu D, Chen X, Xiang Y, et al. LncRNA CCAT1 inhibits cell apoptosis of renal cell carcinoma through up-regulation of Livin protein. Molecular and cellular biochemistry. 2017. [View at Google Scholar]; [View at PubMed].

26. Huang JL, Liao Y, Qiu MX, Li J, An Y. Long non-coding RNA CCAT2 promotes cell proliferation and invasion through regulating Wnt/beta-catenin signaling pathway in clear cell renal cell carcinoma. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine. 2017;39(7):1010428317711314. [View at Google Scholar]; [View at PubMed].

27. Hu G, Dong B, Zhang J, Zhai W, Xie T, Huang B, et al. The long noncoding RNA HOTAIR activates the Hippo pathway by directly binding to SAV1 in renal cell carcinoma. Oncotarget. 2017. [View at Google Scholar].

28. Lu Y, Liu WG, Lu JH, Liu ZJ, Li HB, Liu GJ, et al. LncRNA UCA1 promotes renal cell carcinoma proliferation through epigenetically repressing p21 expression and negatively regulating miR-495. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine. 2017;39(5):1010428317701632. [View at Google Scholar]; [View at PubMed].

29. Wang PQ, Wu YX, Zhong XD, Liu B, Qiao G. Prognostic significance of overexpressed long non-coding RNA TUG1 in patients with clear cell renal cell carcinoma. European review for medical and pharmacological sciences. 2017;21(1):82-6. [View at Google Scholar]; [View at PubMed].

30. He X, Sun F, Guo F, Wang K, Gao Y, Feng Y, et al. Knockdown of Long Noncoding RNA FTX Inhibits Proliferation, Migration, and Invasion in Renal Cell Carcinoma Cells. Oncology research. 2017;25(2):157-66. [View at Publisher]; [View at Google Scholar]; [View at PubMed]; [View at Scopus].

31. Xu Z, Yang F, Wei D, Liu B, Chen C, Bao Y, et al. Long noncoding RNA-SRLR elicits intrinsic sorafenib resistance via evoking IL-6/STAT3 axis in renal cell carcinoma. Oncogene. 2017;36(14):1965-77. [View at Publisher]; [View at Google Scholar]; [View at PubMed]; [View at Scopus].

32. Liu Y, Qian J, Li X, Chen W, Xu A, Zhao K, et al. Long noncoding RNA BX357664 regulates cell proliferation and epithelial-to-mesenchymal transition via inhibition of TGF-beta1/p38/HSP27 signaling in renal cell carcinoma. Oncotarget. 2016;7(49):81410-22. [View at Google Scholar]; [View at PubMed].

33. Xiao HB, Tang K, Liu PJ, Chen K, Hu JH, Zeng J, et al. LncRNA MALAT1 functions as a competing endogenous RNA to regulate ZEB2 expression by sponging miR-200s in clear cell kidney carcinoma. Oncotarget. 2015;6(35):38005-15. [View at Publisher]; [View at Google Scholar]; [View at PubMed]; [View at Scopus].

34. Liu Z, Yan HY, Xia SY, Zhang C, Xiu YC. Downregulation of long non-coding RNA TRIM52-AS1 functions as a tumor suppressor in renal cell carcinoma. Mol Med Rep. 2016;13(4):3206-12. [View at Google Scholar]; [View at PubMed].

35. Wang M, Huang T, Luo G, Huang C, Xiao XY, Wang L, et al. Long non-coding RNA MEG3 induces renal cell carcinoma cells apoptosis by activating the mitochondrial pathway. J Huazhong U Sci-Med. 2015;35(4):541-5. [View at Publisher]; [View at Google Scholar]; [View at Scopus].

36. Xue S, Li QW, Che JP, Guo Y, Yang FQ, Zheng JH. Decreased expression of long non-coding RNA NBAT-1 is associated with poor prognosis in patients with clear cell renal cell carcinoma. Int J Clin Exp Pathol. 2015;8(4):3765-74. [View at Google Scholar]; [View at PubMed].

37. Zhang HM, Yang FQ, Yan Y, Che JP, Zheng JH. High expression of long non-coding RNA SPRY4-IT1 predicts poor prognosis of clear cell renal cell carcinoma. Int J Clin Exp Pathol. 2014;7(9):5801-9. [View at Google Scholar]; [View at PubMed].

38. Cao Q, Wang N, Qi J, Gu Z, Shen H. Long non‑coding RNA‑GAS5 acts as a tumor suppressor in bladder transitional cell carcinoma via regulation of chemokine (C‑C motif) ligand 1 expression. Molecular medicine reports. 2016;13(1):27-34. [View at Publisher]; [View at Google Scholar]; [View at PubMed]; [View at Scopus].

39. Yao J, Chen Y, Wang Y, Liu S, Yuan X, Pan F, et al. Decreased expression of a novel lncRNA CADM1-AS1 is associated with poor prognosis in patients with clear cell renal cell carcinomas. Int J Clin Exp Pathol. 2014;7(6):2758-67. [View at Google Scholar]; [View at PubMed].

40. Thrash-Bingham CA, Tartof KD. aHIF: a natural antisense transcript overexpressed in human renal cancer and during hypoxia. Journal of the National Cancer Institute. 1999;91(2):143-51. [View at Google Scholar].

41. Li JK, Chen C, Liu JY, Shi JZ, Liu SP, Liu B, et al. Long noncoding RNA MRCCAT1 promotes metastasis of clear cell renal cell carcinoma via inhibiting NPR3 and activating p38-MAPK signaling. Mol Cancer. 2017;16(1):111. [View at Google Scholar]; [View at PubMed].

42. Xia M, Yao L, Zhang Q, Wang F, Mei H, Guo X, et al. Long noncoding RNA HOTAIR promotes metastasis of renal cell carcinoma by up-regulating histone H3K27 demethylase JMJD3. Oncotarget. 2017;8(12):19795-802. [View at Google Scholar]; [View at PubMed].

43. Li Y, Wang T, Li Y, Chen D, Yu Z, Jin L, et al. Identification of long-non coding RNA UCA1 as an oncogene in renal cell carcinoma. Mol Med Rep. 2016;13(4):3326-34. [View at Google Scholar]; [View at PubMed].

44. Zhang M, Lu W, Huang Y, Shi J, Wu X, Zhang X, et al. Downregulation of the long noncoding RNA TUG1 inhibits the proliferation, migration, invasion and promotes apoptosis of renal cell carcinoma. Journal of molecular histology. 2016;47(4):421-8. [View at Google Scholar].

45. Xiong J, Liu Y, Jiang L, Zeng Y, Tang W. High expression of long non-coding RNA lncRNA-ATB is correlated with metastases and promotes cell migration and invasion in renal cell carcinoma. Japanese journal of clinical oncology. 2016;46(4):378-84. [View at Google Scholar]; [View at PubMed].

46. Chen S, Ma P, Zhao Y, Li B, Jiang S, Xiong H, et al. Biological function and mechanism of MALAT-1 in renal cell carcinoma proliferation and apoptosis: role of the MALAT-1-Livin protein interaction. The journal of physiological sciences : JPS. 2017;67(5):577-85. [View at Publisher]; [View at Google Scholar]; [View at Scopus].

47. Hirata H, Hinoda Y, Shahryari V, Deng G, Nakajima K, Tabatabai ZL, et al. Long Noncoding RNA MALAT1 Promotes Aggressive Renal Cell Carcinoma through Ezh2 and Interacts with miR-205. Cancer research. 2015;75(7):1322-31. [View at Google Scholar]; [View at PubMed].

48. Song S, Wu Z, Wang C, Liu B, Ye X, Chen J, et al. RCCRT1 is correlated with prognosis and promotes cell migration and invasion in renal cell carcinoma. Urology. 2014;84(3):730 e1-7. [View at Publisher]; [View at Google Scholar]; [View at Scopus].

49. Ni W, Song E, Gong M, Li Y, Yao J, An R. Downregulation of lncRNA SDPR-AS is associated with poor prognosis in renal cell carcinoma. OncoTargets and therapy. 2017;10:3039-47. [View at Publisher]; [View at Google Scholar]; [View at PubMed]; [View at Scopus].

50. Chen JJ, Miao ZJ, Xue BX, Shan YX, Weng GB, Shen BR. Long Non-coding RNAs in Urologic Malignancies: Functional Roles and Clinical Translation. J Cancer. 2016;7(13):1842-55. [View at Publisher]; [View at Google Scholar]; [View at PubMed]; [View at Scopus].

51. Qiao HP, Gao WS, Huo JX, Yang ZS. Long non-coding RNA GAS5 functions as a tumor suppressor in renal cell carcinoma. Asian Pac J Cancer Prev. 2013;14(2):1077-82. [View at Google Scholar]; [View at PubMed].

52. Wang Y, Gao W, Xu J, Zhu Y, Liu L. The long noncoding RNA urothelial carcinoma-associated 1 overexpression as a poor prognostic biomarker in clear cell renal cell carcinoma. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine. 2017;39(5):1010428317698377. [View at Google Scholar].

53. Wang L, Cai Y, Zhao X, Jia X, Zhang J, Liu J, et al. Down-regulated long non-coding RNA H19 inhibits carcinogenesis of renal cell carcinoma. Neoplasma. 2015;62(3):412-8. [View at Google Scholar]; [View at PubMed].

54. Wang J, Xu AM, Zhang JY, He XM, Pan YS, Cheng G, et al. Prognostic significance of long non-coding RNA MALAT-1 in various human carcinomas: a meta-analysis. Genetics and molecular research : GMR. 2016;15(1). [View at Google Scholar].

55. Malouf GG, Zhang J, Yuan Y, Comperat E, Roupret M, Cussenot O, et al. Characterization of long non-coding RNA transcriptome in clear-cell renal cell carcinoma by next-generation deep sequencing. Molecular oncology. 2015;9(1):32-43. [View at Google Scholar]; [View at PubMed].

Paper Title: Long Non-coding RNAs Expression in Renal Cell Carcinoma
Paper Details: Volume 6, Issue 12, Pages: 240-247
Paper doi:10.15412/J.JBTW.01061201
Journal of Biology and Today's World
Journal home page: http://journals.lexispublisher.com/jbtw
Copyright © 2018 Mohammad Taheri et al. This is an open access paper distributed under the Creative Commons Attribution License.
Click here to have/see Comments & Letters to Editor about this paper