Long non-coding RNA BCYRN1 promotes the proliferation and metastasis of cervical cancer via targeting microRNA-138 in vitro and in vivo

Peng,Jie; Hou,Fang; Feng,Jun; Xu,Shui‑Xian; Meng,Xiao‑Yan

doi:10.3892/ol.2018.8015

Long non-coding RNA BCYRN1 promotes the proliferation and metastasis of cervical cancer via targeting microRNA-138 in vitro and in vivo

Authors:
- Jie Peng
- Fang Hou
- Jun Feng
- Shui‑Xian Xu
- Xiao‑Yan Meng
View Affiliations

Affiliations: Department of Obstetrics and Gynecology, Wuzhong People's Hospital, Suzhou, Jiangsu 215128, P.R. China
Published online on: February 9, 2018 https://doi.org/10.3892/ol.2018.8015
Pages: 5809-5818

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

Cervical cancer is one of the most malignant types of tumor and the fourth leading cause of cancer‑associated mortality in females worldwide. High expression of brain cytoplasmic RNA 1 (BCYRN1) has been detected in various tumors. The present study aimed to investigate the effect of BCYRN1 in the viability and motility of cervical cancer, and the relevant mechanism. The results demonstrated that BCYRN1 was upregulated in cervical cancer tissues compared with normal tissues. Elevated levels of BCYRN1 were also detected in three human cervical cancer cell lines (SiHa, HeLa and CaSki) compared with non-cancerous ectocervical epithelial cell line (Ect1/E6E7). The expression of BCYRN1 was suppressed following transfection with small interfering RNA (siRNA) in HeLa cells. The silence of BCYRN1 significantly reduced cell viability and motility. Furthermore, microRNA (miR)‑138 was predicted as a direct target of BCYRN1 and the expression of miR‑138 was elevated in HeLa cells transfected with BCYRN1 siRNA. Subsequently, elevated levels of miR‑138 were suppressed by transfection with miR‑138 inhibitor in HeLa cells pretreated with BCYRN1 siRNA. The targeting association between BCYRN1 and miR‑138 was supported by luciferase reporter assays. Additionally, BCYRN1 siRNA partially counteracted the effect of miR‑138 inhibitor on promoting cell viability and mobility in HeLa cells. Finally, the in vivo experiment verified that BCYRN1 siRNA was able to prevent tumor growth, and reduced the expression of migration marker proteins metalloproteinase 2 and vascular endothelial cell growth factor, with enhanced expression levels of miR‑138. These results suggest that lncRNA BCYRN1 promotes the proliferation and invasion of cervical cancer via targeting miR-138.

View Figures

View References

1	Barra F, Lorusso D, Leone Roberti Maggiore U, Ditto A, Bogani G, Raspagliesi F and Ferrero S: Investigational drugs for the treatment of cervical cancer. Expert Opin Investig Drugs. 26:389–402. 2017. View Article : Google Scholar : PubMed/NCBI
2	PDQ Screening and Prevention Editorial Board: Cervical cancer prevention (PDQ^®): Health professional version = PDQ Cancer Information Summaries. National Cancer Institute; Bethesda, MD: 2002
3	Chen J, Shishkin AA, Zhu X, Kadri S, Maza I, Guttman M, Hanna JH, Regev A and Garber M: Evolutionary analysis across mammals reveals distinct classes of long non-coding RNAs. Genome Biol. 17:192016. View Article : Google Scholar
4	Seles M, Hutterer GC, Kiesslich T, Pummer K, Berindan-Neagoe I, Perakis S, Schwarzenbacher D, Stotz M, Gerger A and Pichler M: Current insights into long non-coding RNAs in renal cell carcinoma. Int J Mol Sci. 17:5732016. View Article : Google Scholar
5	Zheng C, Hao H, Chen L and Shao J: Long noncoding RNAs as novel serum biomarkers for the diagnosis of hepatocellular carcinoma: A systematic review and meta-analysis. Clin Transl Oncol. 19:961–968. 2017. View Article : Google Scholar
6	Gomes CC, de Sousa SF, Calin GA and Gomez RS: The emerging role of long noncoding RNAs in oral cancer. Oral Surg Oral Med Oral Pathol Oral Radiol. 123:235–241. 2017. View Article : Google Scholar
7	Booy EP, McRae EK, Howard R, Deo SR, Ariyo EO, Dzananovic E, Meier M, Stetefeld J and McKenna SA: RNA helicase associated with AU-rich element (RHAU/DHX36) interacts with the 3′-tail of the long non-coding RNA BC200 (BCYRN1). J Biol Chem. 291:5355–5372. 2016. View Article : Google Scholar
8	Hu T and Lu YR: BCYRN1, a c-MYC-activated long non-coding RNA, regulates cell metastasis of non-small-cell lung cancer. Cancer Cell Int. 15:362015. View Article : Google Scholar
9	Zhang XY, Zhang LX, Tian CJ, Tang XY, Zhao LM, Guo YL, Cheng DJ, Chen XL, Ma LJ and Chen ZC: LncRNAs BCYRN1 promoted the proliferation and migration of rat airway smooth muscle cells in asthma via upregulating the expression of transient receptor potential 1. Am J Transl Res. 8:3409–3418. 2016.
10	Lin Y, Liu J, Huang Y, Liu D, Zhang G and Kan H: MicroRNA-489 plays an anti-metastatic role in human hepatocellular carcinoma by targeting matrix metalloproteinase-7. Transl Oncol. 10:211–220. 2017. View Article : Google Scholar
11	Jafri MA, Al-Qahtani MH and Shay JW: Role of miRNAs in human cancer metastasis: Implications for therapeutic intervention. Semin Cancer Biol. 44:117–131. 2017. View Article : Google Scholar
12	Soifer HS, Rossi JJ and Saetrom P: MicroRNAs in disease and potential therapeutic applications. Mol Ther. 15:2070–2079. 2007. View Article : Google Scholar
13	Vrana D, Matzenauer M, Aujesky R, Vrba R, Neoral C, Melichar B and Souček P: Potential predictive role of microRNAs in the neoadjuvant treatment of esophageal cancer. Anticancer Res. 37:403–412. 2017. View Article : Google Scholar
14	Jiang L, Liu X, Kolokythas A, Yu J, Wang A, Heidbreder CE, Shi F and Zhou X: Downregulation of the Rho GTPase signaling pathway is involved in the microRNA-138-mediated inhibition of cell migration and invasion in tongue squamous cell carcinoma. Int J Cancer. 127:505–512. 2010. View Article : Google Scholar
15	O'Donohue MF, Choesmel V, Faubladier M, Fichant G and Gleizes PE: Functional dichotomy of ribosomal proteins during the synthesis of mammalian 40S ribosomal subunits. J Cell Biol. 190:853–866. 2010. View Article : Google Scholar
16	Qi P and Du X: The long non-coding RNAs, a new cancer diagnostic and therapeutic gold mine. Mod Pathol. 26:155–165. 2013. View Article : Google Scholar
17	Prensner JR and Chinnaiyan AM: The emergence of lncRNAs in cancer biology. Cancer Discov. 1:391–407. 2011. View Article : Google Scholar
18	Lin XC, Zhu Y, Chen WB, Lin LW, Chen DH, Huang JR, Pan K, Lin Y, Wu BT, Dai Y and Tu ZG: Integrated analysis of long non-coding RNAs and mRNA expression profiles reveals the potential role of lncRNAs in gastric cancer pathogenesis. Int J Oncol. 45:619–628. 2014. View Article : Google Scholar
19	Zhao M, Ang L, Huang J and Wang J: MicroRNAs regulate the epithelial-mesenchymal transition and influence breast cancer invasion and metastasis. Tumour Biol. 39:1010428317691682. 2017. View Article : Google Scholar
20	Deng B, Zhang Y, Zhang S, Wen F, Miao Y and Guo K: MicroRNA-142-3p inhibits cell proliferation and invasion of cervical cancer cells by targeting FZD7. Tumour Biol. 36:8065–8073. 2015. View Article : Google Scholar
21	Xia YF, Pei GH, Wang N, Che YC, Yu FS, Yin FF, Liu HX, Luo B and Wang YK: miR-3156-3p is downregulated in HPV-positive cervical cancer and performs as a tumor-suppressive miRNA. Virol J. 14:202017. View Article : Google Scholar
22	Wang Q, Zhong M, Liu W, Li J, Huang J and Zheng L: Alterations of microRNAs in cisplatin-resistant human non-small cell lung cancer cells (A549/DDP). Exp Lung Res. 37:427–434. 2011. View Article : Google Scholar
23	Zhao X, Yang L, Hu J and Ruan J: miR-138 might reverse multidrug resistance of leukemia cells. Leuk Res. 34:1078–1082. 2010. View Article : Google Scholar
24	Zhou N, Fei D, Zong S, Zhang M and Yue Y: MicroRNA-138 inhibits proliferation, migration and invasion through targeting hTERT in cervical cancer. Oncol Lett. 12:3633–3639. 2016. View Article : Google Scholar
25	Li B, Yang XX, Wang D and Ji HK: MicroRNA-138 inhibits proliferation of cervical cancer cells by targeting c-Met. Eur Rev Med Pharmacol Sci. 20:1109–1114. 2016.
26	Liz J and Esteller M: lncRNAs and microRNAs with a role in cancer development. Biochim Biophys Acta. 1859:169–176. 2016. View Article : Google Scholar
27	Wang J, Liu X, Wu H, Ni P, Gu Z, Qiao Y, Chen N, Sun F and Fan Q: CREB up-regulates long non-coding RNA, HULC expression through interaction with microRNA-372 in liver cancer. Nucleic Acids Res. 38:5366–5383. 2010. View Article : Google Scholar
28	Ma MZ, Chu BF, Zhang Y, Weng MZ, Qin YY, Gong W and Quan ZW: Long non-coding RNA CCAT1 promotes gallbladder cancer development via negative modulation of miRNA-218-5p. Cell Death Dis. 6:e15832015. View Article : Google Scholar
29	Braconi C, Kogure T, Valeri N, Huang N, Nuovo G, Costinean S, Negrini M, Miotto E, Croce CM and Patel T: MicroRNA-29 can regulate expression of the long non-coding RNA gene MEG3 in hepatocellular cancer. Oncogene. 30:4750–4756. 2011. View Article : Google Scholar
30	Lu H, He Y, Lin L, Qi Z, Ma L, Li L and Su Y: Long non-coding RNA MALAT1 modulates radiosensitivity of HR-HPV⁺ cervical cancer via sponging miR-145. Tumour Biology. 37:1683–1691. 2016. View Article : Google Scholar