lncRNA LINC00963 downregulation regulates colorectal cancer tumorigenesis and progression via the miR‑10b/FGF13 axis

Wu,Yujin; Cong,Longling; Chen,Wenjian; Wang,Xuechuan; Qiu,Fanghua

doi:10.3892/mmr.2021.11850

lncRNA LINC00963 downregulation regulates colorectal cancer tumorigenesis and progression via the miR‑10b/FGF13 axis

Authors:
- Yujin Wu
- Longling Cong
- Wenjian Chen
- Xuechuan Wang
- Fanghua Qiu
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Affiliations: Department of Gastroenterology, The Affiliated TCM Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510130, P.R. China, Department of Hospital Infection Control, The Affiliated TCM Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510130, P.R. China
Published online on: January 18, 2021 https://doi.org/10.3892/mmr.2021.11850
Article Number: 211
Copyright: © Wu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Long non-coding RNAs (lncRNAs) serve a key role in different types of cancer, including colorectal cancer (CRC). The exact roles and mechanisms underlying lncRNA00963 [long intergenic non‑protein coding RNA 963 (LINC00963)] in CRC are not completely understood. The present study aimed to identify the effects and mechanisms underlying LINC00963 in CRC. Firstly, the LINC00963 expression was detected using reverse transcription‑quantitative PCR and the results demonstrated that LINC00963 expression levels were significantly increased in CRC tissues and cell lines compared with healthy tissues and HpoEpiC cells, respectively. Online database analysis indicated that high levels of LINC00963 were associated with low survival rates. The results of functional experiments, such as CCK‑8 assay, colony formation assay, wound healing assay and Transwell invasion assay, indicated that LINC00963 knockdown significantly inhibited CRC cell proliferation, colony formation, migration and invasion compared with the small interfering RNA (si)‑negative control (NC) group. Furthermore, the luciferase reporter indicated that LINC00963 competitively regulated microRNA (miR)‑10b by targeting fibroblast growth factor 13 (FGF13). Compared with si‑NC, LINC00963 knockdown decreased the expression levels of FGF13, vimentin and N‑cadherin, and increased the expression of E‑cadherin as detecting by western blotting. miR‑10b inhibitors partly attenuated si‑LINC00963‑induced inhibition of CRC cell proliferation, migration and invasion. Collectively, the results of the present study suggested a potential role of the LINC00963/miR-10b/FGF13 axis in the tumorigenesis and progression of CRC, indicating a novel lncRNA-based diagnostic or therapeutic target for CRC.

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1	Wu C: Systemic therapy for colon cancer. Surg Oncol Clin N Am. 27:235–242. 2018. View Article : Google Scholar : PubMed/NCBI
2	Marotta G, Muto T, Benincasa G and De Monaco A: Formyl peptide receptor 2 mediated chemotherapeutics drug resistance in colon cancer cells. Point of view from pharmacogenetics field. Eur Rev Med Pharmacol Sci. 22:1178–1179. 2018.PubMed/NCBI
3	Schreuders EH, Ruco A, Rabeneck L, Schoen RE, Sung JJ, Young GP and Kuipers EJ: Colorectal cancer screening: A global overview of existing programmes. Gut. 64:1637–1649. 2015. View Article : Google Scholar : PubMed/NCBI
4	Dueland S, Hagness M, Line PD, Guren TK, Tveit KM and Foss A: Is liver transplantation an option in colorectal cancer patients with nonresectable liver metastases and progression on all lines of standard chemotherapy? Ann Surg Oncol. 22:2195–2200. 2015. View Article : Google Scholar : PubMed/NCBI
5	Cleven AH, Derks S, Draht MX, Smits KM, Melotte V, Van Neste L, Tournier B, Jooste V, Chapusot C, Weijenberg MP, et al: CHFR promoter methylation indicates poor prognosis in stage II microsatellite stable colorectal cancer. Clin Cancer Res. 20:3261–3271. 2014. View Article : Google Scholar : PubMed/NCBI
6	Chen P, Xi Q, Wang Q and Wei P: Downregulation of microRNA-100 correlates with tumor progression and poor prognosis in colorectal cancer. Med Oncol. 31:2352014. View Article : Google Scholar : PubMed/NCBI
7	Yang G, Lu X and Yuan L: lncRNA: A link between RNA and cancer. Biochim Biophys Acta. 1839:1097–1109. 2014. View Article : Google Scholar : PubMed/NCBI
8	Jarroux J, Morillon A and Pinskaya M: History, discovery, and classification of lncRNAs. Adv Exp Med Biol. 1008:1–46. 2017. View Article : Google Scholar : PubMed/NCBI
9	Akhade VS, Pal D and Kanduri C: Long noncoding RNA: Genome organization and mechanism of action. Adv Exp Med Biol. 1008:47–74. 2017. View Article : Google Scholar : PubMed/NCBI
10	Guttman M, Russell P, Ingolia NT, Weissman JS and Lander ES: Ribosome profiling provides evidence that large noncoding RNAs do not encode proteins. Cell. 154:240–251. 2013. View Article : Google Scholar : PubMed/NCBI
11	Rinn JL and Chang HY: Genome regulation by long noncoding RNAs. Annu Rev Biochem. 81:145–166. 2012. View Article : Google Scholar : PubMed/NCBI
12	Zhao W, Geng D, Li S, Chen Z and Sun M: lncRNA HOTAIR influences cell growth, migration, invasion, and apoptosis via the miR-20a-5p/HMGA2 axis in breast cancer. Cancer Med. 7:842–855. 2018. View Article : Google Scholar : PubMed/NCBI
13	Jiang N, Meng X, Mi H, Chi Y, Li S, Jin Z, Tian H, He J, Shen W, Tian H, et al: Circulating lncRNA XLOC_009167 serves as a diagnostic biomarker to predict lung cancer. Clin Chim Acta. 486:26–33. 2018. View Article : Google Scholar : PubMed/NCBI
14	Han Q, Xu L, Lin W, Yao X, Jiang M, Zhou R, Sun X and Zhao L: Long noncoding RNA CRCMSL suppresses tumor invasive and metastasis in colorectal carcinoma through nucleocytoplasmic shuttling of HMGB2. Oncogene. 38:3019–3032. 2019. View Article : Google Scholar : PubMed/NCBI
15	Huang L, Lin H, Kang L, Huang P, Huang J, Cai J, Xian Z, Zhu P, Huang M, Wang L, et al: Aberrant expression of long noncoding RNA SNHG15 correlates with liver metastasis and poor survival in colorectal cancer. J Cell Physiol. 234:7032–7039. 2019. View Article : Google Scholar : PubMed/NCBI
16	Shi J, Zhong X, Song Y, Wu Z, Gao P, Zhao J, Sun J, Wang J, Liu J and Wang Z: Long non-coding RNA RUNX1-IT1 plays a tumour-suppressive role in colorectal cancer by inhibiting cell proliferation and migration. Cell Biochem Funct. 37:11–20. 2019. View Article : Google Scholar : PubMed/NCBI
17	Liu Y, Yang Y, Li L, Liu Y, Geng P, Li G and Song H: lncRNA SNHG1 enhances cell proliferation, migration, and invasion in cervical cancer. Biochem Cell Biol. 96:38–43. 2018. View Article : Google Scholar : PubMed/NCBI
18	Li Z, Qin X, Bian W, Li Y, Shan B, Yao Z and Li S: Exosomal lncRNA ZFAS1 regulates esophageal squamous cell carcinoma cell proliferation, invasion, migration and apoptosis via microRNA-124/STAT3 axis. J Exp Clin Cancer Res. 38:4772019. View Article : Google Scholar : PubMed/NCBI
19	Jin FS, Wang HM and Song XY: Long non-coding RNA TCF7 predicts the progression and facilitates the growth and metastasis of colorectal cancer. Mol Med Rep. 17:6902–6908. 2018.PubMed/NCBI
20	Di Cecilia S, Zhang F, Sancho A, Li S, Aguiló F, Sun Y, Rengasamy M, Zhang W, Del Vecchio L, Salvatore F, et al: RBM5-AS1 is critical for self-renewal of colon cancer stem-like cells. Cancer Res. 76:5615–5627. 2016. View Article : Google Scholar : PubMed/NCBI
21	Wang L, Cho KB, Li Y, Tao G, Xie Z and Guo B: Long noncoding RNA (lncRNA)-mediated competing endogenous RNA networks provide novel potential biomarkers and therapeutic targets for colorectal cancer. Int J Mol Sci. 20:57582019. View Article : Google Scholar
22	Fan CN, Ma L and Liu N: Systematic analysis of lncRNA-miRNA-mRNA competing endogenous RNA network identifies four-lncRNA signature as a prognostic biomarker for breast cancer. J Transl Med. 16:2642018. View Article : Google Scholar : PubMed/NCBI
23	Wu JH, Tian XY, An QM, Guan XY and Hao CY: LINC00963 promotes hepatocellular carcinoma progression by activating PI3K/AKT pathway. Eur Rev Med Pharmacol Sci. 22:1645–1652. 2018.PubMed/NCBI
24	Zhang N, Zeng X, Sun C, Guo H, Wang T, Wei L, Zhang Y, Zhao J and Ma X: lncRNA LINC00963 promotes tumorigenesis and radioresistance in breast cancer by sponging miR-324-3p and inducing ACK1 expression. Mol Ther Nucleic Acids. 18:871–881. 2019. View Article : Google Scholar : PubMed/NCBI
25	Wang J, Li C, Xu L, Yang C and Zhang X: miR-1193 was sponged by LINC00963 and inhibited cutaneous squamous cell carcinoma progression by targeting SOX4. Pathol Res Pract. 215:1526002019. View Article : Google Scholar : PubMed/NCBI
26	Zhou Y, Yin L, Li H, Liu LH and Xiao T: The lncRNA LINC00963 facilitates osteosarcoma proliferation and invasion by suppressing miR-204-3p/FN1 axis. Cancer Biol Ther. 20:1141–1148. 2019. View Article : Google Scholar : PubMed/NCBI
27	Jiao H, Jiang S, Wang H, Li Y and Zhang W: Upregulation of LINC00963 facilitates melanoma progression through miR-608/NACC1 pathway and predicts poor prognosis. Biochem Biophys Res Commun. 504:34–39. 2018. View Article : Google Scholar : PubMed/NCBI
28	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
29	Song JJ and Li W: miR-10b suppresses the growth and metastasis of colorectal cancer cell by targeting FGF13. Eur Rev Med Pharmacol Sci. 23:576–587. 2019.PubMed/NCBI
30	Esteller M: Non-coding RNAs in human disease. Nat Rev Genet. 12:861–874. 2011. View Article : Google Scholar : PubMed/NCBI
31	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 : PubMed/NCBI
32	Slack FJ and Chinnaiyan AM: The role of non-coding RNAs in oncology. Cell. 179:1033–1055. 2019. View Article : Google Scholar : PubMed/NCBI
33	Kopp F and Mendell JT: Functional classification and experimental dissection of long noncoding RNAs. Cell. 172:393–407. 2018. View Article : Google Scholar : PubMed/NCBI
34	van Heesch S, van Iterson M, Jacobi J, Boymans S, Essers PB, de Bruijn E, Hao W, MacInnes AW, Cuppen E and Simonis M: Extensive localization of long noncoding RNAs to the cytosol and mono- and polyribosomal complexes. Genome Biol. 15:R62014. View Article : Google Scholar : PubMed/NCBI
35	Evans JR, Feng FY and Chinnaiyan AM: The bright side of dark matter: lncRNAs in cancer. J Clin Invest. 126:2775–2782. 2016. View Article : Google Scholar : PubMed/NCBI
36	Lin C and Yang L: Long noncoding RNA in cancer: Wiring signaling circuitry. Trends Cell Biol. 28:287–301. 2018. View Article : Google Scholar : PubMed/NCBI
37	Sullenger BA and Nair S: From the RNA world to the clinic. Science. 352:1417–1420. 2016. View Article : Google Scholar : PubMed/NCBI
38	Wang L, Han S, Jin G, Zhou X, Li M, Ying X, Wang L, Wu H and Zhu Q: Linc00963: A novel, long non-coding RNA involved in the transition of prostate cancer from androgen-dependence to androgen-independence. Int J Oncol. 44:2041–2049. 2014. View Article : Google Scholar : PubMed/NCBI
39	Yu T, Zhao Y, Hu Z, Li J, Chu D, Zhang J, Li Z, Chen B, Zhang X, Pan H, et al: Metalnc9 facilitates lung cancer metastasis via a PGK1-activated AKT/mTOR pathway. Cancer Res. 77:5782–5794. 2017. View Article : Google Scholar : PubMed/NCBI
40	Cesana M, Cacchiarelli D, Legnini I, Santini T, Sthandier O, Chinappi M, Tramontano A and Bozzoni I: A long noncoding RNA controls muscle differentiation by functioning as a competing endogenous RNA. Cell. 147:358–369. 2011. View Article : Google Scholar : PubMed/NCBI
41	Bak RO and Mikkelsen JG: miRNA sponges: Soaking up miRNAs for regulation of gene expression. Wiley Interdiscip Rev RNA. 5:317–333. 2014. View Article : Google Scholar : PubMed/NCBI
42	Dey BK, Mueller AC and Dutta A: Long non-coding RNAs as emerging regulators of differentiation, development, and disease. Transcription. 5:e9440142014. View Article : Google Scholar : PubMed/NCBI
43	Kartha RV and Subramanian S: Competing endogenous RNAs (ceRNAs): New entrants to the intricacies of gene regulation. Front Genet. 5:82014. View Article : Google Scholar : PubMed/NCBI
44	Saliminejad K, Khorram Khorshid HR, Soleymani Fard S and Ghaffari SH: An overview of microRNAs: Biology, functions, therapeutics, and analysis methods. J Cell Physiol. 234:5451–5465. 2019. View Article : Google Scholar : PubMed/NCBI
45	Hoek K, Rimm DL, Williams KR, Zhao H, Ariyan S, Lin A, Kluger HM, Berger AJ, Cheng E and Trombetta ES: Expression profiling reveals novel pathways in the transformation of melanocytes to melanomas. Cancer Res. 64:5270–5282. 2004. View Article : Google Scholar : PubMed/NCBI
46	Missiaglia E, Dalai I, Barbi S, Beghelli S, Falconi M, della Peruta M, Piemonti L, Capurso G, Di Florio A, delle Fave G, et al: Pancreatic endocrine tumors: expression profiling evidences a role for AKT-mTOR pathway. J Clin Oncol. 28:245–255. 2010. View Article : Google Scholar : PubMed/NCBI
47	Bublik DR, Bursać S, Sheffer M, Oršolić I, Shalit T, Tarcic O, Kotler E, Mouhadeb O, Hoffman Y, Fuchs G, et al: Regulatory module involving FGF13, miR-504, and p53 regulates ribosomal biogenesis and supports cancer cell survival. Proc Natl Acad Sci USA. 114:E496–E505. 2017. View Article : Google Scholar : PubMed/NCBI