LncRNA CDKN2B‑AS1 sponges miR‑28‑5p to regulate proliferation and inhibit apoptosis in colorectal cancer

Ma,Mei-Li; Zhang,Hong-Yan; Zhang,Shu-Yi; Yi,Xiao-Li

doi:10.3892/or.2021.8164

LncRNA CDKN2B‑AS1 sponges miR‑28‑5p to regulate proliferation and inhibit apoptosis in colorectal cancer

Authors:
- Mei-Li Ma
- Hong-Yan Zhang
- Shu-Yi Zhang
- Xiao-Li Yi
View Affiliations

Affiliations: Department of Oncology, Qingdao Municipal Hospital (Group), Qingdao, Shandong 266011, P.R. China, Department of Oncology, Qingdao ChengYang People's Hospital, Qingdao, Shandong 266000, P.R. China, Department of Radiology, Qingdao Haici Medical Group, Qingdao, Shandong 266034, P.R. China
Published online on: August 2, 2021 https://doi.org/10.3892/or.2021.8164
Article Number: 213

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 noncoding RNA (lncRNA) CDKN2B‑antisense RNA 1 (AS1) functions as a tumor oncogene in numerous cancers. However, the roles and mechanism of CDKN2B‑AS1 in colorectal cancer (CRC) have not been explored. The present study aimed to investigate whether and how CDKN2B‑AS1 contributes to CRC progression. The data revealed that CDKN2B‑AS1 expression was upregulated in CRC tissues. Loss‑of‑function assays demonstrated that CDKN2B‑AS1 in CRC modulated cell proliferation and apoptosis, which was mediated by cyclin D1, cyclin‑dependent kinase (CDK) 4, p‑Rb, caspase‑9 and caspase‑3. Bioinformatics analysis and luciferase reporter assays indicated direct binding of microRNA (miR)‑28‑5p to CDKN2B‑AS1. Moreover, the results herein revealed that the expression of miR‑28‑5p was negatively correlated with that of CDKN2B‑AS1 in CRC tissue. Moreover, CDKN2B‑AS1 acted as a miR‑28‑5p competing endogenous RNA (ceRNA) to target and regulate the expression of URGCP. These findings indicated that CDKN2B‑AS1 plays roles in CRC progression, providing a potential therapeutic target or novel diagnostic biomarker for CRC.

View Figures

View References

1	Nindra U, Shahnam A and Mahon KL: Review of systemic chemotherapy in unresectable colorectal peritoneal carcinomatosis. Asia-Pac J Clin Oncol. Feb 19–2021.(Epub ahead of print). View Article : Google Scholar : PubMed/NCBI
2	Grady WM and Carethers JM: Genomic and epigenetic instability in colorectal cancer pathogenesis. Gastroenterology. 135:1079–1099. 2008. View Article : Google Scholar : PubMed/NCBI
3	Oldenhuis CN, Oosting SF, Gietema JA and de Vries EG: Prognostic versus predictive value of biomarkers in oncology. Eur J Cancer. 44:946–953. 2008. View Article : Google Scholar : PubMed/NCBI
4	Huarte M, Guttman M, Feldser D, Garber M, Koziol MJ, Kenzelmann-Broz D, Khalil AM, Zuk O, Amit I, Rabani M, et al: A large intergenic noncoding RNA induced by p53 mediates global gene repression in the p53 response. Cell. 142:409–419. 2010. View Article : Google Scholar : PubMed/NCBI
5	Tang Y, Tang R, Tang M, Huang P, Liao Z, Zhou J, Zhou L, Su M, Chen P, Jiang J, et al: LncRNA DNAJC3-AS1 regulates fatty acid synthase via the EGFR pathway to promote the progression of colorectal cancer. Front Oncol. 10:6045342020. View Article : Google Scholar : PubMed/NCBI
6	Nagano T and Fraser P: No-nonsense functions for long noncoding RNAs. Cell. 145:178–181. 2011. View Article : Google Scholar : PubMed/NCBI
7	Dinger ME, Pang KC, Mercer TR and Mattick JS: Differentiating protein-coding and noncoding RNA: Challenges and ambiguities. PLoS Comput Bbiol. 4:e10001762008. View Article : Google Scholar : PubMed/NCBI
8	Dasgupta P, Kulkarni P, Majid S, Hashimoto Y, Shiina M, Shahryari V, Bhat NS, Tabatabai L, Yamamura S, Saini S, et al: LncRNA CDKN2B-AS1/miR-141/cyclin D network regulates tumor progression and metastasis of renal cell carcinoma. Cell Death Dis. 11:6602020. View Article : Google Scholar : PubMed/NCBI
9	Song C, Qi Y, Zhang J, Guo C and Yuan C: CDKN2B-AS1: An indispensable long non-coding RNA in multiple diseases. Curr Pharm Des. 26:5335–5346. 2020. View Article : Google Scholar : PubMed/NCBI
10	Liu F, Xiao Y, Ma L and Wang J: Regulating of cell cycle progression by the lncRNA CDKN2B-AS1/miR-324-5p/ROCK1 axis in laryngeal squamous cell cancer. Int J Biol Markers. 35:47–56. 2020. View Article : Google Scholar : PubMed/NCBI
11	Dos Santos IL, Penna KGBD, Dos Santos Carneiro MA, Libera LSD, Ramos JEP and Saddi VA: Tissue micro-RNAs associated with colorectal cancer prognosis: A systematic review. Mol Biol Rep. 48:1853–1867. 2021. View Article : Google Scholar : PubMed/NCBI
12	Tay Y, Rinn J and Pandolfi PP: The multilayered complexity of ceRNA crosstalk and competition. Nature. 505:344–352. 2014. View Article : Google Scholar : PubMed/NCBI
13	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 : PubMed/NCBI
14	Andrisani O: Epigenetic mechanisms in hepatitis B virus-associated hepatocellular carcinoma. Hepatoma Res. 7:122021.PubMed/NCBI
15	Zukerman R, Harris A, Vercellin AV, Siesky B, Pasquale LR and Ciulla TA: Molecular genetics of glaucoma: Subtype and ethnicity considerations. Genes (Basel). 12:552020. View Article : Google Scholar : PubMed/NCBI
16	Luo Y, Tao H, Jin L, Xiang W and Guo W: CDKN2B-AS1 exerts oncogenic role in osteosarcoma by promoting cell proliferation and epithelial to mesenchymal transition. Cancer Biother Radiopharm. 35:58–65. 2020. View Article : Google Scholar : PubMed/NCBI
17	Rathi S, Danford I, Gudiseva HV, Verkuil L, Pistilli M, Vishwakarma S, Kaur I, Dave T, O'Brien JM and Chavali VRM: Molecular genetics and functional analysis implicate CDKN2BAS1-CDKN2B involvement in POAG pathogenesis. Cells. 9:19342020. View Article : Google Scholar : PubMed/NCBI
18	Akbari F, Peymani M, Salehzadeh A and Ghaedi K: Integrative in silico and in vitro transcriptomics analysis revealed new lncRNAs related to intrinsic apoptotic genes in colorectal cancer. Cancer Cell Int. 20:5462020. View Article : Google Scholar : PubMed/NCBI
19	Chiron D, Martin P, Di Liberto M, Huang X, Ely S, Lannutti BJ, Leonard JP, Mason CE and Chen-Kiang S: Induction of prolonged early G1 arrest by CDK4/CDK6 inhibition reprograms lymphoma cells for durable PI3Kδ inhibition through PIK3IP1. Cell Cycle. 12:1892–1900. 2013. View Article : Google Scholar : PubMed/NCBI
20	Gogolin S, Ehemann V, Becker G, Brueckner LM, Dreidax D, Bannert S, Nolte I, Savelyeva L, Bell E and Westermann F: CDK4 inhibition restores G(1)-S arrest in MYCN-amplified neuroblastoma cells in the context of doxorubicin-induced DNA damage. Cell Cycle. 12:1091–1104. 2013. View Article : Google Scholar : PubMed/NCBI
21	Girouard J, Lafleur MJ, Parent S, Leblanc V and Asselin E: Involvement of Akt isoforms in chemoresistance of endometrial carcinoma cells. Gynecol Oncol. 128:335–343. 2013. View Article : Google Scholar : PubMed/NCBI
22	Smillie CL, Sirey T and Ponting CP: Complexities of post-transcriptional regulation and the modeling of ceRNA crosstalk. Crit Rev Biochem Mol Biol. 53:231–245. 2018. View Article : Google Scholar : PubMed/NCBI
23	Tian L, Han F, Yang J, Ming X and Chen L: Long noncoding RNA LINC01006 exhibits oncogenic properties in cervical cancer by functioning as a molecular sponge for microRNA285p and increasing PAK2 expression. Int J Mol Med. 47:462021. View Article : Google Scholar : PubMed/NCBI
24	Wu W, He K, Guo Q, Chen J, Zhang M, Huang K, Yang D, Wu L, Deng Y, Luo X, et al: SSRP1 promotes colorectal cancer progression and is negatively regulated by miR-28-5p. J Cell Mol Med. 23:3118–3129. 2019. View Article : Google Scholar : PubMed/NCBI
25	Fazio S, Berti G, Russo F, Evangelista M, D'Aurizio R, Mercatanti A, Pellegrini M and Rizzo M: The miR-28-5p targetome discovery identified SREBF2 as one of the mediators of the miR-28-5p tumor suppressor activity in prostate cancer cells. Cells. 9:3542020. View Article : Google Scholar : PubMed/NCBI
26	Proença MA, Biselli JM, Succi M, Severino FE, Berardinelli GN, Caetano A, Reis RM, Hughes DJ and Silva AE: Relationship between Fusobacterium nucleatum, inflammatory mediators and microRNAs in colorectal carcinogenesis. World J Gastroenterol. 24:5351–5365. 2018. View Article : Google Scholar : PubMed/NCBI
27	Huang J, Zhu B, Lu L, Lian Z, Wang Y, Yang X, Satiroglu-Tufan NL, Liu J and Luo Z: The expression of novel gene URG4 in osteosarcoma: Correlation with patients' prognosis. Pathology. 41:149–154. 2009. View Article : Google Scholar : PubMed/NCBI
28	Qiu T, Wang K, Li X and Jin J: miR-671-5p inhibits gastric cancer cell proliferation and promotes cell apoptosis by targeting URGCP. Exp Ther Med. 16:4753–4758. 2018.PubMed/NCBI
29	Xing S, Zhang B, Hua R, Tai WC, Zeng Z, Xie B, Huang C, Xue J, Xiong S, Yang J, et al: URG4/URGCP enhances the angiogenic capacity of human hepatocellular carcinoma cells in vitro via activation of the NF-κB signaling pathway. BMC Cancer. 15:3682015. View Article : Google Scholar : PubMed/NCBI
30	Shan TD, Tian ZB, Li Q, Jiang YP, Liu FG, Sun XG, Han Y, Sun LJ and Chen L: Long intergenic noncoding RNA 00908 promotes proliferation and inhibits apoptosis of colorectal cancer cells by regulating KLF5 expression. J Cell Physiol. 236:889–899. 2021. View Article : Google Scholar : PubMed/NCBI
31	Liu HZ, Shan TD, Han Y and Liu XS: Silencing long non-coding RNA CASC9 inhibits colorectal cancer cell proliferation by acting as a competing endogenous RNA of miR-576-5p to regulate AKT3. Cell Death Discov. 6:1152020. View Article : Google Scholar : PubMed/NCBI
32	Piao HY, Guo S, Jin H, Wang Y and Zhang J: LINC00184 involved in the regulatory network of ANGPT2 via ceRNA mediated miR-145 inhibition in gastric cancer. J Cancer. 12:2336–2350. 2021. View Article : Google Scholar : PubMed/NCBI
33	Lee WJ, Shin CH, Ji H, Jeong SD, Park MS, Won HH, Pandey PR, Tsitsipatis D, Gorospe M and Kim HH: hnRNPK-regulated LINC00263 promotes malignant phenotypes through miR-147a/CAPN2. Cell Death Dis. 12:2902021. View Article : Google Scholar : PubMed/NCBI