BANCR contributes to the growth and invasion of melanoma by functioning as a competing endogenous RNA to upregulate Notch2 expression by sponging miR‑204

Cai,Bingjie; Zheng,Yunpeng; Ma,Shanshan; Xing,Qu; Wang,Xinxin; Yang,Bo; Yin,Guangwen; Guan,Fangxia

doi:10.3892/ijo.2017.4173

BANCR contributes to the growth and invasion of melanoma by functioning as a competing endogenous RNA to upregulate Notch2 expression by sponging miR‑204

Authors:
- Bingjie Cai
- Yunpeng Zheng
- Shanshan Ma
- Qu Xing
- Xinxin Wang
- Bo Yang
- Guangwen Yin
- Fangxia Guan
View Affiliations

Affiliations: The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China, School of Life Sciences, Zhengzhou University, Zhengzhou, Henan 450001, P.R. China
Published online on: October 23, 2017 https://doi.org/10.3892/ijo.2017.4173
Pages: 1941-1951

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

BRAF-activated non-coding RNA (BANCR) is a long non-coding RNA (lncRNA) that contributes to the initiation and development of many solid tumors, including melanoma. However, the BANCR functions and downstream mechanisms are largely unknown. In this study, we aim to investigate how BANCR participates in the proliferation and migration of malignant melanoma and elucidate the underlying mechanism in this process. We found that the expression of the BANCR was low in melanocytic nevus and human melanocytes but high in melanoma tissues and cell lines. Knockdown of BANCR inhibited melanoma cell proliferation and invasion, and induced cell apoptosis. The decreased expression of relative marker proteins further demonstrated the inhibitory effect of BANCR siRNA in cell growth and migration. Then, we detected downregulation of microRNA-204 (miR‑204), a suppressor of melanoma growth, in melanoma tissues and cell lines. We identified that miR‑204 was a direct target of BANCR and neurogenic locus notch homolog protein 2 (Notch2) was a direct target of miR‑204. BANCR may promote melanoma cell growth through inhibition of miR‑204, leading to the activation of Notch2 pathway. By tumorigenicity assay in BALB/c nude mice, we further demonstrated that BANCR knockdown inhibited tumor growth in vivo. Our results suggest the BANCR/miR‑204/Notch2 axis mediates melanoma cell proliferation and tumor progression.

View Figures

View References

1	Siegel RL, Miller KD and Jemal A: Cancer statistics, 2016. CA Cancer J Clin. 66:7–30. 2016. View Article : Google Scholar : PubMed/NCBI
2	Linares MA, Zakaria A and Nizran P: Skin cancer. Prim Care. 42:645–659. 2015. View Article : Google Scholar : PubMed/NCBI
3	Singh S, Zafar A, Khan S and Naseem I: Towards therapeutic advances in melanoma management: An overview. Life Sci. 174:50–58. 2017. View Article : Google Scholar : PubMed/NCBI
4	Gray-Schopfer V, Wellbrock C and Marais R: Melanoma biology and new targeted therapy. Nature. 445:851–857. 2007. View Article : Google Scholar : PubMed/NCBI
5	Gros A, Parkhurst MR, Tran E, Pasetto A, Robbins PF, Ilyas S, Prickett TD, Gartner JJ, Crystal JS, Roberts IM, et al: Prospective identification of neoantigen-specific lymphocytes in the peripheral blood of melanoma patients. Nat Med. 22:433–438. 2016. View Article : Google Scholar : PubMed/NCBI
6	Slominski AT and Carlson JA: Melanoma resistance: A bright future for academicians and a challenge for patient advocates. Mayo Clin Proc. 89:429–433. 2014. View Article : Google Scholar : PubMed/NCBI
7	Shah DJ and Dronca RS: Latest advances in chemotherapeutic, targeted, and immune approaches in the treatment of metastatic melanoma. Mayo Clin Proc. 89:504–519. 2014. View Article : Google Scholar : PubMed/NCBI
8	Smith MA and Mattick JS: Structural and functional annotation of long noncoding RNAs. Methods Mol Biol. 1526:65–85. 2017. View Article : Google Scholar
9	Batista PJ and Chang HY: Long noncoding RNAs: Cellular address codes in development and disease. Cell. 152:1298–1307. 2013. View Article : Google Scholar : PubMed/NCBI
10	Martens-Uzunova ES, Böttcher R, Croce CM, Jenster G, Visakorpi T and Calin GA: Long noncoding RNA in prostate, bladder, and kidney cancer. Eur Urol. 65:1140–1151. 2014. View Article : Google Scholar : PubMed/NCBI
11	Sun M, Xia R, Jin F, Xu T, Liu Z, De W and Liu X: Downregulated long noncoding RNA MEG3 is associated with poor prognosis and promotes cell proliferation in gastric cancer. Tumour Biol. 35:1065–1073. 2014. View Article : Google Scholar
12	Sun M, Jin FY, Xia R, Kong R, Li JH, Xu TP, Liu YW, Zhang EB, Liu XH and De W: Decreased expression of long noncoding RNA GAS5 indicates a poor prognosis and promotes cell proliferation in gastric cancer. BMC Cancer. 14:3192014. View Article : Google Scholar : PubMed/NCBI
13	Cai X, Liu Y, Yang W, Xia Y, Yang C, Yang S and Liu X: Long noncoding RNA MALAT1 as a potential therapeutic target in osteosarcoma. J Orthop Res. 34:932–941. 2016. View Article : Google Scholar
14	Guo Q, Zhao Y, Chen J, Hu J, Wang S, Zhang D and Sun Y: BRAF-activated long non-coding RNA contributes to colorectal cancer migration by inducing epithelial-mesenchymal transition. Oncol Lett. 8:869–875. 2014.PubMed/NCBI
15	Sun M, Liu XH, Wang KM, Nie FQ, Kong R, Yang JS, Xia R, Xu TP, Jin FY, Liu ZJ, et al: Downregulation of BRAF activated non-coding RNA is associated with poor prognosis for non-small cell lung cancer and promotes metastasis by affecting epithelial-mesenchymal transition. Mol Cancer. 13:682014. View Article : Google Scholar : PubMed/NCBI
16	Wang Y, Guo Q, Zhao Y, Chen J, Wang S, Hu J and Sun Y: BRAF-activated long non-coding RNA contributes to cell proliferation and activates autophagy in papillary thyroid carcinoma. Oncol Lett. 8:1947–1952. 2014.PubMed/NCBI
17	Li R, Zhang L, Jia L, Duan Y, Li Y, Bao L and Sha N: Long non-coding RNA BANCR promotes proliferation in malignant melanoma by regulating MAPK pathway activation. PLoS One. 9:e1008932014. View Article : Google Scholar : PubMed/NCBI
18	Leucci E, Coe EA, Marine JC and Vance KW: The emerging role of long non-coding RNAs in cutaneous melanoma. Pigment Cell Melanoma Res. 29:619–626. 2016. View Article : Google Scholar : PubMed/NCBI
19	Philippidou D, Schmitt M, Moser D, Margue C, Nazarov PV, Muller A, Vallar L, Nashan D, Behrmann I and Kreis S: Signatures of microRNAs and selected microRNA target genes in human melanoma. Cancer Res. 70:4163–4173. 2010. View Article : Google Scholar : PubMed/NCBI
20	Wang D, Wang D, Wang N, Long Z and Ren X: Long non-coding RNA BANCR promotes endometrial cancer cell proliferation and Invasion by regulating MMP2 and MMP1 via ERK/MAPK signaling pathway. Cell Physiol Biochem. 40:644–656. 2016. View Article : Google Scholar : PubMed/NCBI
21	Lv L, Jia JQ and Chen J: LncRNA CCAT1 upregulates proliferation and invasion in melanoma cells via suppressing miR-33a. Oncol Res. Apr 12–2017.Epub ahead of print. View Article : Google Scholar : 2017.PubMed/NCBI
22	Sun Y, Cheng H, Wang G, Yu G, Zhang D, Wang Y, Fan W and Yang W: Deregulation of miR-183 promotes melanoma development via lncRNA MALAT1 regulation and ITGB1 signal activation. Oncotarget. 8:3509–3518. 2017.
23	Massi D, Tarantini F, Franchi A, Paglierani M, Di Serio C, Pellerito S, Leoncini G, Cirino G, Geppetti P and Santucci M: Evidence for differential expression of Notch receptors and their ligands in melanocytic nevi and cutaneous malignant melanoma. Modern Pathol. 19:246–254. 2006. View Article : Google Scholar
24	Suliman MA, Zhang Z, Na H, Ribeiro AL, Zhang Y, Niang B, Hamid AS, Zhang H, Xu L and Zuo Y: Niclosamide inhibits colon cancer progression through downregulation of the Notch pathway and upregulation of the tumor suppressor miR-200 family. Int J Mol Med. 38:776–784. 2016. View Article : Google Scholar : PubMed/NCBI
25	Chegeni S, Khaki Z, Shirani D, Vajhi A, Taheri M, Tamrchi Y and Rostami A: Investigation of MMP-2 and MMP-9 activities in canine sera with dilated cardiomyopathy. Iran J Vet Res. 16:182–187. 2015.
26	Mikhaylova O, Stratton Y, Hall D, Kellner E, Ehmer B, Drew AF, Gallo CA, Plas DR, Biesiada J, Meller J, et al: VHL-regulated miR-204 suppresses tumor growth through inhibition of LC3B-mediated autophagy in renal clear cell carcinoma. Cancer Cell. 21:532–546. 2012. View Article : Google Scholar : PubMed/NCBI
27	Bao W, Wang HH, Tian FJ, He XY, Qiu MT, Wang JY, Zhang HJ, Wang LH and Wan XP: A TrkB-STAT3-miR-204-5p regulatory circuitry controls proliferation and invasion of endometrial carcinoma cells. Mol Cancer. 12:1552013. View Article : Google Scholar : PubMed/NCBI
28	Yin Y, Zhang B, Wang W, Fei B, Quan C, Zhang J, Song M, Bian Z, Wang Q, Ni S, et al: miR-204-5p inhibits proliferation and invasion and enhances chemotherapeutic sensitivity of colorectal cancer cells by downregulating RAB22A. Clin Cancer Res. 20:6187–6199. 2014. View Article : Google Scholar : PubMed/NCBI
29	Fatica A and Bozzoni I: Long non-coding RNAs: New players in cell differentiation and development. Nat Rev Genet. 15:7–21. 2014. View Article : Google Scholar
30	Shi X, Sun M, Liu H, Yao Y and Song Y: Long non-coding RNAs: A new frontier in the study of human diseases. Cancer Lett. 339:159–166. 2013. View Article : Google Scholar : PubMed/NCBI
31	Berrondo C, Flax J, Kucherov V, Siebert A, Osinski T, Rosenberg A, Fucile C, Richheimer S and Beckham CJ: Expression of the long non-coding RNA HOTAIR correlates with disease progression in bladder cancer and is contained in bladder cancer patient urinary exosomes. PLoS One. 11:e01472362016. View Article : Google Scholar : PubMed/NCBI
32	Schmidt K, Joyce CE, Buquicchio F, Brown A, Ritz J, Distel RJ, Yoon CH and Novina CD: The lncRNA SLNCR1 mediates melanoma invasion through a conserved SRA1-like region. Cell Rep. 15:2025–2037. 2016. View Article : Google Scholar : PubMed/NCBI
33	Khaitan D, Dinger ME, Mazar J, Crawford J, Smith MA, Mattick JS and Perera RJ: The melanoma-upregulated long noncoding RNA SPRY4-IT1 modulates apoptosis and invasion. Cancer Res. 71:3852–3862. 2011. View Article : Google Scholar : PubMed/NCBI
34	Garzon R, Calin GA and Croce CM: MicroRNAs in cancer. Annu Rev Med. 60:167–179. 2009. View Article : Google Scholar : PubMed/NCBI
35	Li T, Pan H and Li R: The dual regulatory role of miR-204 in cancer. Tumour Biol. 37:11667–11677. 2016. View Article : Google Scholar : PubMed/NCBI
36	Ding M, Lin B, Li T, Liu Y, Li Y, Zhou X, Miao M, Gu J, Pan H, Yang F, et al: A dual yet opposite growth-regulating function of miR-204 and its target XRN1 in prostate adenocarcinoma cells and neuroendocrine-like prostate cancer cells. Oncotarget. 6:7686–7700. 2015. View Article : Google Scholar : PubMed/NCBI
37	Tan X, Huang Z and Li X: Long Non-coding RNA MALAT1 interacts with miR-204 to modulate human hilar cholangiocarcinoma proliferation, migration, and invasion by targeting CXCR4. J Cell Biochem. 118:3643–3653. 2017. View Article : Google Scholar : PubMed/NCBI
38	Maillard I, Fang T and Pear WS: Regulation of lymphoid development, differentiation, and function by the Notch pathway. Annu Rev Immunol. 23:945–974. 2005. View Article : Google Scholar : PubMed/NCBI
39	Schouwey K, Aydin IT, Radtke F and Beermann F: RBP-Jκ-dependent Notch signaling enhances retinal pigment epithelial cell proliferation in transgenic mice. Oncogene. 30:313–322. 2011. View Article : Google Scholar
40	Asnaghi L, Ebrahimi KB, Schreck KC, Bar EE, Coonfield ML, Bell WR, Handa J, Merbs SL, Harbour JW and Eberhart CG: Notch signaling promotes growth and invasion in uveal melanoma. Clin Cancer Res. 18:654–665. 2012. View Article : Google Scholar : PubMed/NCBI
41	Forloni M, Dogra SK, Dong Y, Conte D Jr, Ou J, Zhu LJ, Deng A, Mahalingam M, Green MR and Wajapeyee N: miR-146a promotes the initiation and progression of melanoma by activating Notch signaling. eLife. 3:e014602014. View Article : Google Scholar : PubMed/NCBI