Knockdown of long non-coding RNA metastasis associated lung adenocarcinoma transcript 1 inhibits the proliferation and migration of bladder cancer cells by modulating the microRNA-34a/cyclin D1 axis

Liu,Ye; Gao,Saiyue; Du,Qingyan; Zhao,Qingsong

doi:10.3892/ijmm.2018.3959

Knockdown of long non-coding RNA metastasis associated lung adenocarcinoma transcript 1 inhibits the proliferation and migration of bladder cancer cells by modulating the microRNA-34a/cyclin D1 axis

Authors:
- Ye Liu
- Saiyue Gao
- Qingyan Du
- Qingsong Zhao
View Affiliations

Affiliations: Clinical Laboratory, Jining No.1 People's Hospital, Jining, Shandong 272011, P.R. China, Physical Examination Laboratory, Linyi Lanshan District Center for Disease Control and Prevention, Linyi, Shandong 276000, P.R. China, Department of Urology, Jining No.1 People's Hospital, Jining, Shandong 272011, P.R. China
Published online on: October 29, 2018 https://doi.org/10.3892/ijmm.2018.3959
Pages: 547-556

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Long non‑coding RNA (lncRNA) metastasis associated lung adenocarcinoma transcript 1 (MALAT1) has been demonstrated to participate in the development and progression of some common cancer types, including bladder cancer (BC). However, the regulatory mechanism of MALAT1 underlying BC growth and metastasis remains to be fully elucidated. The present study revealed that MALAT1 was significantly upregulated in BC tissues and cell lines compared with the adjacent non‑tumour tissues and the normal urinary tract epithelial cell line SV‑HUC‑1, respectively. The expression levels of MALAT1 were higher in stage III‑IV BC tissues when compared with that in stage I‑II tissues. Furthermore, knockdown of MALAT1 significantly inhibited BC cell proliferation and migration by targeting microRNA (miR)‑34a. The expression levels of miR‑34a were significantly decreased in BC tissues and cell lines compared with that of adjacent non‑tumour tissues and SV‑HUC‑1 cells. In addition, the expression of miR‑34a was inversely correlated with the expression of MALAT1 in BC tissues. The present study revealed that cyclin D1 (CCND1) was identified as a target gene of miR‑34a, and its expression was negatively mediated by miR‑34a in BC cells. Notably, the upregulation of CCND1 impaired the effect of MALAT1 inhibition on BC cell proliferation and migration. In addition, the expression levels of CCND1 were significantly increased in BC tissues and cell lines. In conclusion, the present findings demonstrated that the knockdown of lncRNA MALAT1 inhibits the proliferation and migration of BC cells by modulating the miR‑34a/CCND1 axis, suggesting that the MALAT1/miR‑34a/CCND1 axis may be a potential therapeutic target for BC treatment.

View Figures

View References

1	Siegel RL, Miller KD and Jemal A: Cancer statistics, 2015. CA Cancer J Clin. 65:5–29. 2015. View Article : Google Scholar : PubMed/NCBI
2	Skeldon SC and Larry Goldenberg S: Bladder cancer: A portal into mens health. Urol Oncol. 33:40–44. 2015. View Article : Google Scholar
3	Sathe A and Nawroth R: Targeting the PI3K/AKT/mTOR pathway in bladder cancer. Methods Mol Biol. 1655:335–350. 2018. View Article : Google Scholar
4	Zhou Y, Meng X, Chen S, Li W, Li D, Singer R and Gu W: IMP1 regulates UCA1-mediated cell invasion through facilitating UCA1 decay and decreasing the sponge effect of UCA1 for miR-122-5p. Breast Cancer Res. 20:322018. View Article : Google Scholar : PubMed/NCBI
5	Smolle MA and Pichler M: The role of long non-coding RNAs in osteosarcoma. Noncoding RNA. 4:E72018.PubMed/NCBI
6	Ruan X: Long noncoding RNA central of glucose homeostasis. J Cell Biochem. 117:1061–1065. 2016. View Article : Google Scholar
7	Wapinski O and Chang HY: Long noncoding RNAs and human disease. Trends Cell Biol. 21:354–361. 2011. View Article : Google Scholar : PubMed/NCBI
8	Zhai X and Xu W: Long noncoding RNA ATB promotes proliferation, migration and invasion in bladder cancer by suppressing microRNA-126. Oncol Res. 26:1063–1072. 2018. View Article : Google Scholar : PubMed/NCBI
9	Xu R, Zhu X, Chen F, Huang C, Ai K, Wu H, Zhang L and Zhao X: LncRNA XIST/miR-200c regulates the stemness properties and tumourigenicity of human bladder cancer stem cell-like cells. Cancer Cell Int. 18:412018. View Article : Google Scholar : PubMed/NCBI
10	Peng Z, Liu C and Wu M: New insights into long noncoding RNAs and their roles in glioma. Mol Cancer. 17:612018. View Article : Google Scholar : PubMed/NCBI
11	Zhang Y, Dai Q, Zeng F and Liu H: MALAT1 Promotes the proliferation and metastasis of osteosarcoma cells by activating the Rac1/JNK pathway via targeting miR-509. Oncol Res. Apr 27–2018.Epub ahead of print. View Article : Google Scholar
12	Liu S, Song L, Zeng S and Zhang L: MALAT1-miR-124-RBG2 axis is involved in growth and invasion of HR-HPV-positive cervical cancer cells. Tumour Biol. 37:633–640. 2016. View Article : Google Scholar
13	Ji Q, Liu X, Fu X, Zhang L, Sui H, Zhou L, Sun J, Cai J, Qin J, Ren J and Li Q: Resveratrol inhibits invasion and metastasis of colorectal cancer cells via MALAT1 mediated Wnt/beta-catenin signal pathway. PLoS One. 8:e787002013. View Article : Google Scholar
14	Hirata H, Hinoda Y, Shahryari V, Deng G, Nakajima K, Tabatabai ZL, Ishii N and Dahiya R: Long noncoding RNA MALAT1 promotes aggressive renal cell carcinoma through Ezh2 and interacts with miR-205. Cancer Res. 75:1322–1331. 2015. View Article : Google Scholar : PubMed/NCBI
15	Ying L, Chen Q, Wang Y, Zhou Z, Huang Y and Qiu F: Upregulated MALAT-1 contributes to bladder cancer cell migration by inducing epithelial-to-mesenchymal transition. Mol Biosyst. 8:2289–2294. 2012. View Article : Google Scholar : PubMed/NCBI
16	Li C, Cui Y, Liu LF, Ren WB, Li QQ, Zhou X, Li YL, Li Y, Bai XY and Zu XB: High expression of long noncoding RNA MALAT1 indicates a poor prognosis and promotes clinical progression and metastasis in bladder cancer. Clin Genitourin Cancer. 15:570–576. 2017. View Article : Google Scholar : PubMed/NCBI
17	Xie H, Liao X, Chen Z, Fang Y, He A, Zhong Y, Gao Q, Xiao H, Li J, Huang W and Liu Y: LncRNA MALAT1 inhibits apoptosis and promotes invasion by antagonizing miR-125b in bladder cancer cells. J Cancer. 8:3803–3811. 2017. View Article : Google Scholar : PubMed/NCBI
18	Farazi TA, Hoell JI, Morozov P and Tuschl T: MicroRNAs in human cancer. Adv Exp Med Biol. 774:1–20. 2013. View Article : Google Scholar : PubMed/NCBI
19	Garg D and Cohen SM: miRNAs and aging: A genetic perspective. Ageing Res Rev. 17:3–8. 2014. View Article : Google Scholar : PubMed/NCBI
20	Boon RA and Vickers KC: Intercellular transport of microRNAs. Arterioscler Thromb Vasc Biol. 33:186–192. 2013. View Article : Google Scholar : PubMed/NCBI
21	Hwang HW and Mendell JT: MicroRNAs in cell proliferation, cell death, and tumorigenesis. Br J Cancer. 94:776–780. 2006. View Article : Google Scholar : PubMed/NCBI
22	Ma ZL, Hou PP, Li YL, Wang DT, Yuan TW, Wei JL, Zhao BT, Lou JT, Zhao XT, Jin Y and Jin YX: MicroRNA-34a inhibits the proliferation and promotes the apoptosis of non-small cell lung cancer H1299 cell line by targeting TGFbetaR2. Tumour Biol. 36:2481–2490. 2015. View Article : Google Scholar
23	Wu X, Zhong D, Gao Q, Zhai W, Ding Z and Wu J: MicroRNA-34a inhibits human osteosarcoma proliferation by downregulating ether a go-go 1 expression. Int J Med Sci. 10:676–682. 2013. View Article : Google Scholar :
24	Yu G, Yao W, Xiao W, Li H, Xu H and Lang B: MicroRNA-34a functions as an anti-metastatic microRNA and suppresses angiogenesis in bladder cancer by directly targeting CD44. J Exp Clin Cancer Res. 33:7792014. View Article : Google Scholar
25	Sun H, Tian J, Xian W, Xie T and Yang X: miR-34a inhibits proliferation and invasion of bladder cancer cells by targeting orphan nuclear receptor HNF4G. Dis Markers. 2015:8792542015. View Article : Google Scholar : PubMed/NCBI
26	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar
27	Wang M, Guo C, Wang L, Luo G, Huang C, Li Y, Liu D, Zeng F, Jiang G and Xiao X: Long noncoding RNA GAS5 promotes bladder cancer cells apoptosis through inhibiting EZH2 transcription. Cell Death Dis. 9:2382018. View Article : Google Scholar : PubMed/NCBI
28	Jiao D, Li Z, Zhu M, Wang Y, Wu G and Han X: LncRNA MALAT1 promotes tumor growth and metastasis by targeting miR-124/foxq1 in bladder transitional cell carcinoma (BTCC). Am J Cancer Res. 8:748–760. 2018.PubMed/NCBI
29	Xie CH, Cao YM, Huang Y, Shi QW, Guo JH, Fan ZW, Li JG, Chen BW and Wu BY: Long non-coding RNA TUG1 contributes to tumorigenesis of human osteosarcoma by sponging miR-9-5p and regulating POU2F1 expression. Tumour Biol. 37:15031–15041. 2016. View Article : Google Scholar : PubMed/NCBI
30	Li C, Wan L, Liu Z, Xu G, Wang S, Su Z, Zhang Y, Zhang C, Liu X, Lei Z and Zhang HT: Long non-coding RNA XIST promotes TGF-beta-induced epithelial-mesenchymal transition by regulating miR-367/141-ZEB2 axis in non-small-cell lung cancer. Cancer Lett. 418:185–195. 2018. View Article : Google Scholar : PubMed/NCBI
31	Yan G, Wang X, Yang M, Lu L and Zhou Q: Long non-coding RNA TUG1 promotes progression of oral squamous cell carcinoma through upregulating FMNL2 by sponging miR-219. Am J Cancer Res. 7:1899–1912. 2017.PubMed/NCBI
32	Ye J, Li L, Feng P, Wan J and Li J: Downregulation of miR-34a contributes to the proliferation and migration of laryngeal carcinoma cells by targeting cyclin D1. Oncol Rep. 36:390–398. 2016. View Article : Google Scholar : PubMed/NCBI
33	Sun F, Fu H, Liu Q, Tie Y, Zhu J, Xing R, Sun Z and Zheng X: Downregulation of CCND1 and CDK6 by miR-34a induces cell cycle arrest. FEBS Lett. 582:1564–1568. 2008. View Article : Google Scholar : PubMed/NCBI