Comprehensive analysis of the aberrantly expressed profiles of lncRNAs, miRNAs and the regulation network of the associated ceRNAs in clear cell renal cell carcinoma_Journal of Biomedical Engineering

Authors：

HOU Wanting ^1,2 , TANG Qiulin ² ,  BI Feng ^1,2

1. Department of Abdominal Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, P.R.China;
2. Laboratory of Molecular Targeted Therapy in Oncology, West China Hospital, Sichuan University, Chengdu 610041, P.R.China;

Corresponding author：

BI Feng, Email: bifeng@scu.edu.cn

Keywords：

clear cell renal cell carcinoma; The Cancer Genome Atlas; long noncoding RNA; competing endogenous RNA; microRNA

DOI：

10.7507/1001-5515.201801057

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

To evaluate the differential expression profiles of the lncRNAs, miRNAs, mRNAs and ceRNAs, and their implication in the prognosis in clear cell renal cell carcinoma (CCRCC), the large sample genomics analysis technologies were used in this study. The RNA and miRNA sequencing data of CCRCC were obtained from The Cancer Genome Atlas (TCGA) database, and R software was used for gene expression analysis and survival analysis. Cytoscape software was used to construct the ceRNA network. The results showed that a total of 1 570 lncRNAs, 54 miRNAs, and 17 mRNAs were differentially expressed in CCRCC, and most of their expression levels were up-regulated (false discovery rate < 0.01 and absolute log fold change > 2). The ceRNA regulatory network showed the interaction between 89 differentially expressed lncRNAs and 9 differentially expressed miRNAs. Further survival analysis revealed that 38 lncRNAs (including COL18A1-AS1, TCL6, LINC00475, UCA1, WT1-AS, HOTTIP, PVT1, etc.) and 2 miRNAs (including miR-21 and miR-155) were correlated with the overall survival time of CCRCC (P < 0.05). Together, this study provided us several new evidences for the targeted therapy and prognosis assessment of CCRCC.

Citation： HOU Wanting, TANG Qiulin, BI Feng. Comprehensive analysis of the aberrantly expressed profiles of lncRNAs, miRNAs and the regulation network of the associated ceRNAs in clear cell renal cell carcinoma. Journal of Biomedical Engineering, 2019, 36(2): 267-273. doi: 10.7507/1001-5515.201801057 Copy

1.	Moch H. An overview of renal cell cancer: pathology and genetics. Semin Cancer Biol, 2013, 23(1): 3-9.
2.	Wolff I, May M, Hoschke B, et al. Do we need new high-risk criteria for surgically treated renal cancer patients to improve the outcome of future clinical trials in the adjuvant setting? Results of a comprehensive analysis based on the multicenter CORONA database. Eur J Surg Oncol, 2016, 42(5): 744-750.
3.	Motzer R J, Escudier B, Mcdermott D F, et al. Nivolumab versus Everolimus in advanced renal-cell carcinoma. N Engl J Med, 2015, 373(19): 1803-1813.
4.	Motzer R J, Hutson T E, McCann L, et al. Overall survival in renal-cell carcinoma with pazopanib versus sunitinib. N Engl J Med, 2014, 370(18): 1769-1770.
5.	Lau N C, Lim L P, Weinstein E G, et al. An abundant class of tiny RNAs with probable regulatory roles in Caenorhabditis elegans. Science, 2001, 294(5543): 858-862.
6.	Prensner J R, Chinnaiyan A M. The emergence of lncRNAs in cancer biology. Cancer Discov, 2011, 1(5): 391-407.
7.	Cesana M, Cacchiarelli D, Legnini I, et al. A long noncoding RNA controls muscle differentiation by functioning as a competing endogenous RNA. Cell, 2011, 147(2): 358-369.
8.	Zhang Jian, Fan Dahua, Jian Zhixiang, et al. Cancer specific long noncoding RNAs show differential expression patterns and competing endogenous RNA potential in hepatocellular carcinoma. PLoS One, 2015, 10(10): e0141042.
9.	Xia Tian, Liao Qi, Jiang Xiaoming, et al. Long noncoding RNA associated-competing endogenous RNAs in gastric cancer. Sci Rep, 2014, 4: 6088.
10.	Luan Tian, Zhang Ximei, Wang Shuyuan, et al. Long non-coding RNA MIAT promotes breast cancer progression and functions as ceRNA to regulate DUSP7 expression by sponging miR-155-5p. Oncotarget, 2017, 8(44): 76153-76164.
11.	Zhou Meng, Diao Zhiyong, Yue Xiaolong, et al. Construction and analysis of dysregulated lncRNA-associated ceRNA network identified novel lncRNA biomarkers for early diagnosis of human pancreatic cancer. Oncotarget, 2016, 7(35): 56383-56394.
12.	Huang Chuiguo, Yuan Naijun, Wu Liying, et al. An integrated analysis for long noncoding RNAs and microRNAs with the mediated competing endogenous RNA network in papillary renal cell carcinoma. Onco Targets Ther, 2017, 10: 4037-4050.
13.	Zhou W, Ye X L, Xu J, et al. The lncRNA H19 mediates breast cancer cell plasticity during EMT and MET plasticity by differentially sponging miR-200b/c and let-7b. Sci Signal, 2017, 10: 483.
14.	Hirata H, Hinoda Y, Shahryari V, et al. Long noncoding RNA MALAT1 promotes aggressive renal cell carcinoma through Ezh2 and interacts with miR-205. Cancer Res, 2015, 75(7): 1322-1331.
15.	He H T, Xu M, Kuang Y, et al. Biomarker and competing endogenous RNA potential of tumor-specific long noncoding RNA in chromophobe renal cell carcinoma. Onco Targets Ther, 2016, 9: 6399-6406.
16.	Feng Ling, Wang Ru, Lian Meng, et al. Integrated analysis of long noncoding RNA and mRNA expression profile in advanced laryngeal squamous cell carcinoma. PLoS One, 2016, 11(12): e0169232.
17.	Lv Long, Chen G, Zhou Jianping, et al. WT1-AS promotes cell apoptosis in hepatocellular carcinoma through down-regulating of WT1. J Exp Clin Cancer Res, 2015, 34: 119.
18.	Su Hengchuan, Sun Tiantian, Wang Hongkai, et al. Decreased TCL6 expression is associated with poor prognosis in patients with clear cell renal cell carcinoma. Oncotarget, 2017, 8(4): 5789-5799.
19.	Bao Xu, Duan Junyao, Yan Yongji, et al. Upregulation of long noncoding RNA PVT1 predicts unfavorable prognosis in patients with clear cell renal cell carcinoma. Cancer Biomark, 2017, 21(1): 55-63.
20.	Yang Tao, Zhou Hui, Liu Peijun, et al. lncRNA PVT1 and its splicing variant function as competing endogenous RNA to regulate clear cell renal cell carcinoma progression. Oncotarget, 2017, 8(49): 85353-85367.
21.	Yang Yali, Ren Mingxin, Song Chao, et al. LINC00461, a long non-coding RNA, is important for the proliferation and migration of glioma cells. Oncotarget, 2017, 8(48): 84123-84139.
22.	Lan Tian, Ma Weijie, Hong Zhenfei, et al. Long non-coding RNA small nucleolar RNA host gene 12 (SNHG12) promotes tumorigenesis and metastasis by targeting miR-199a/b-5p in hepatocellular carcinoma. J Exp Clin Cancer Res, 2017, 36(1): 11.
23.	Wang J Z, Xu C L, Wu H, et al. LncRNA SNHG12 promotes cell growth and inhibits cell apoptosis in colorectal cancer cells. Braz J Med Biol Res, 2017, 50(3): e6079.
24.	Zhang Hanyun, Lu Wenjie. LncRNA SNHG12 regulates gastric cancer progression by acting as a molecular sponge of miR-320. Mol Med Rep, 2018, 17(2): 2743-2749.
25.	Lai I L, Yang C A, Lin P C, et al. Long noncoding RNA MIAT promotes non-small cell lung cancer proliferation and metastasis through MMP9 activation. Oncotarget, 2017, 8(58): 98148-98162.
26.	Wang Li, Chen Zhenhong, An Li, et al. Analysis of long non-coding RNA expression profiles in non-small cell lung cancer. Cell Physiol Biochem, 2016, 38(6): 2389-2400.
27.	Cancer Genome Atlas Research Network. Comprehensive molecular characterization of clear cell renal cell carcinoma. Nature, 2013, 499(7456): 43-49.
28.	Ahrend H, Kaul A, Ziegler S, et al. MicroRNA-1 and MicroRNA-21 individually regulate cellular growth of non-malignant and malignant renal cells. In Vivo, 2017, 31(4): 625-630.
29.	Fritz H K, Lindgren D, Ljungberg B A, et al. The miR(21/10b) ratio as a prognostic marker in clear cell renal cell carcinoma. Eur J Cancer, 2014, 50(10): 1758-1765.
30.	Zhang Guangjun, Xiao Huaxu, Tian Hongpeng, et al. Upregulation of microRNA-155 promotes the migration and invasion of colorectal cancer cells through the regulation of claudin-1 expression. Int J Mol Med, 2013, 31(6): 1375-1380.
31.	Yan Xinlong, Jia Yali, Chen Lin, et al. Hepatocellular carcinoma-associated mesenchymal stem cells promote hepatocarcinoma progression: role of the S100A4-miR155-SOCS1-MMP9 axis. Hepatology, 2013, 57(6): 2274-2286.
32.	Shi Da, Qu Qinghua, Chang Qimeng, et al. A five-long non-coding RNA signature to improve prognosis prediction of clear cell renal cell carcinoma. Oncotarget, 2017, 8(35): 58699-58708.
33.	Yang Feiyan, Wang Yan, Wu J G, et al. Analysis of long non-coding RNA expression profiles in clear cell renal cell carcinoma. Oncol Lett, 2017, 14(3): 2757-2764.
34.	Liu G, Ye Z, Zhao X, et al. SP1-induced up-regulation of lncRNA SNHG14 as a ceRNA promotes migration and invasion of clear cell renal cell carcinoma by regulating N-WASP. Am J Cancer Res, 2017, 7(12): 2515-2525.
35.	Hong Quan, Li Ou, Zheng Wei, et al. LncRNA HOTAIR regulates HIF-1 alpha/AXL signaling through inhibition of miR-217 in renal cell carcinoma. Cell Death Dis, 2017, 8(5): e2772.
36.	Cao Yunjie, Xu Renfang, Xu Xianlin, et al. Downregulation of lncRNA CASC2 by microRNA-21 increases the proliferation and migration of renal cell carcinoma cells. Mol Med Rep, 2016, 14(1): 1019-1025.

1. Moch H. An overview of renal cell cancer: pathology and genetics. Semin Cancer Biol, 2013, 23(1): 3-9.
2. Wolff I, May M, Hoschke B, et al. Do we need new high-risk criteria for surgically treated renal cancer patients to improve the outcome of future clinical trials in the adjuvant setting? Results of a comprehensive analysis based on the multicenter CORONA database. Eur J Surg Oncol, 2016, 42(5): 744-750.
3. Motzer R J, Escudier B, Mcdermott D F, et al. Nivolumab versus Everolimus in advanced renal-cell carcinoma. N Engl J Med, 2015, 373(19): 1803-1813.
4. Motzer R J, Hutson T E, McCann L, et al. Overall survival in renal-cell carcinoma with pazopanib versus sunitinib. N Engl J Med, 2014, 370(18): 1769-1770.
5. Lau N C, Lim L P, Weinstein E G, et al. An abundant class of tiny RNAs with probable regulatory roles in Caenorhabditis elegans. Science, 2001, 294(5543): 858-862.
6. Prensner J R, Chinnaiyan A M. The emergence of lncRNAs in cancer biology. Cancer Discov, 2011, 1(5): 391-407.
7. Cesana M, Cacchiarelli D, Legnini I, et al. A long noncoding RNA controls muscle differentiation by functioning as a competing endogenous RNA. Cell, 2011, 147(2): 358-369.
8. Zhang Jian, Fan Dahua, Jian Zhixiang, et al. Cancer specific long noncoding RNAs show differential expression patterns and competing endogenous RNA potential in hepatocellular carcinoma. PLoS One, 2015, 10(10): e0141042.
9. Xia Tian, Liao Qi, Jiang Xiaoming, et al. Long noncoding RNA associated-competing endogenous RNAs in gastric cancer. Sci Rep, 2014, 4: 6088.
10. Luan Tian, Zhang Ximei, Wang Shuyuan, et al. Long non-coding RNA MIAT promotes breast cancer progression and functions as ceRNA to regulate DUSP7 expression by sponging miR-155-5p. Oncotarget, 2017, 8(44): 76153-76164.
11. Zhou Meng, Diao Zhiyong, Yue Xiaolong, et al. Construction and analysis of dysregulated lncRNA-associated ceRNA network identified novel lncRNA biomarkers for early diagnosis of human pancreatic cancer. Oncotarget, 2016, 7(35): 56383-56394.
12. Huang Chuiguo, Yuan Naijun, Wu Liying, et al. An integrated analysis for long noncoding RNAs and microRNAs with the mediated competing endogenous RNA network in papillary renal cell carcinoma. Onco Targets Ther, 2017, 10: 4037-4050.
13. Zhou W, Ye X L, Xu J, et al. The lncRNA H19 mediates breast cancer cell plasticity during EMT and MET plasticity by differentially sponging miR-200b/c and let-7b. Sci Signal, 2017, 10: 483.
14. Hirata H, Hinoda Y, Shahryari V, et al. Long noncoding RNA MALAT1 promotes aggressive renal cell carcinoma through Ezh2 and interacts with miR-205. Cancer Res, 2015, 75(7): 1322-1331.
15. He H T, Xu M, Kuang Y, et al. Biomarker and competing endogenous RNA potential of tumor-specific long noncoding RNA in chromophobe renal cell carcinoma. Onco Targets Ther, 2016, 9: 6399-6406.
16. Feng Ling, Wang Ru, Lian Meng, et al. Integrated analysis of long noncoding RNA and mRNA expression profile in advanced laryngeal squamous cell carcinoma. PLoS One, 2016, 11(12): e0169232.
17. Lv Long, Chen G, Zhou Jianping, et al. WT1-AS promotes cell apoptosis in hepatocellular carcinoma through down-regulating of WT1. J Exp Clin Cancer Res, 2015, 34: 119.
18. Su Hengchuan, Sun Tiantian, Wang Hongkai, et al. Decreased TCL6 expression is associated with poor prognosis in patients with clear cell renal cell carcinoma. Oncotarget, 2017, 8(4): 5789-5799.
19. Bao Xu, Duan Junyao, Yan Yongji, et al. Upregulation of long noncoding RNA PVT1 predicts unfavorable prognosis in patients with clear cell renal cell carcinoma. Cancer Biomark, 2017, 21(1): 55-63.
20. Yang Tao, Zhou Hui, Liu Peijun, et al. lncRNA PVT1 and its splicing variant function as competing endogenous RNA to regulate clear cell renal cell carcinoma progression. Oncotarget, 2017, 8(49): 85353-85367.
21. Yang Yali, Ren Mingxin, Song Chao, et al. LINC00461, a long non-coding RNA, is important for the proliferation and migration of glioma cells. Oncotarget, 2017, 8(48): 84123-84139.
22. Lan Tian, Ma Weijie, Hong Zhenfei, et al. Long non-coding RNA small nucleolar RNA host gene 12 (SNHG12) promotes tumorigenesis and metastasis by targeting miR-199a/b-5p in hepatocellular carcinoma. J Exp Clin Cancer Res, 2017, 36(1): 11.
23. Wang J Z, Xu C L, Wu H, et al. LncRNA SNHG12 promotes cell growth and inhibits cell apoptosis in colorectal cancer cells. Braz J Med Biol Res, 2017, 50(3): e6079.
24. Zhang Hanyun, Lu Wenjie. LncRNA SNHG12 regulates gastric cancer progression by acting as a molecular sponge of miR-320. Mol Med Rep, 2018, 17(2): 2743-2749.
25. Lai I L, Yang C A, Lin P C, et al. Long noncoding RNA MIAT promotes non-small cell lung cancer proliferation and metastasis through MMP9 activation. Oncotarget, 2017, 8(58): 98148-98162.
26. Wang Li, Chen Zhenhong, An Li, et al. Analysis of long non-coding RNA expression profiles in non-small cell lung cancer. Cell Physiol Biochem, 2016, 38(6): 2389-2400.
27. Cancer Genome Atlas Research Network. Comprehensive molecular characterization of clear cell renal cell carcinoma. Nature, 2013, 499(7456): 43-49.
28. Ahrend H, Kaul A, Ziegler S, et al. MicroRNA-1 and MicroRNA-21 individually regulate cellular growth of non-malignant and malignant renal cells. In Vivo, 2017, 31(4): 625-630.
29. Fritz H K, Lindgren D, Ljungberg B A, et al. The miR(21/10b) ratio as a prognostic marker in clear cell renal cell carcinoma. Eur J Cancer, 2014, 50(10): 1758-1765.
30. Zhang Guangjun, Xiao Huaxu, Tian Hongpeng, et al. Upregulation of microRNA-155 promotes the migration and invasion of colorectal cancer cells through the regulation of claudin-1 expression. Int J Mol Med, 2013, 31(6): 1375-1380.
31. Yan Xinlong, Jia Yali, Chen Lin, et al. Hepatocellular carcinoma-associated mesenchymal stem cells promote hepatocarcinoma progression: role of the S100A4-miR155-SOCS1-MMP9 axis. Hepatology, 2013, 57(6): 2274-2286.
32. Shi Da, Qu Qinghua, Chang Qimeng, et al. A five-long non-coding RNA signature to improve prognosis prediction of clear cell renal cell carcinoma. Oncotarget, 2017, 8(35): 58699-58708.
33. Yang Feiyan, Wang Yan, Wu J G, et al. Analysis of long non-coding RNA expression profiles in clear cell renal cell carcinoma. Oncol Lett, 2017, 14(3): 2757-2764.
34. Liu G, Ye Z, Zhao X, et al. SP1-induced up-regulation of lncRNA SNHG14 as a ceRNA promotes migration and invasion of clear cell renal cell carcinoma by regulating N-WASP. Am J Cancer Res, 2017, 7(12): 2515-2525.
35. Hong Quan, Li Ou, Zheng Wei, et al. LncRNA HOTAIR regulates HIF-1 alpha/AXL signaling through inhibition of miR-217 in renal cell carcinoma. Cell Death Dis, 2017, 8(5): e2772.
36. Cao Yunjie, Xu Renfang, Xu Xianlin, et al. Downregulation of lncRNA CASC2 by microRNA-21 increases the proliferation and migration of renal cell carcinoma cells. Mol Med Rep, 2016, 14(1): 1019-1025.

Journal of Biomedical Engineering

Comprehensive analysis of the aberrantly expressed profiles of lncRNAs, miRNAs and the regulation network of the associated ceRNAs in clear cell renal cell carcinoma

Abstract Full text Figures/Tables Video References Cited by

Previous Article

Next Article

Format

Content