LncRNA CCAT1 negatively regulates miR‑181a‑5p to promote endometrial carcinoma cell proliferation and migration

Yu,Jing; Jiang,Lijuan; Gao,Yutao; Sun,Qijian; Liu,Beibei; Hu,Yong; Han,Xuesong

doi:10.3892/etm.2019.7422

LncRNA CCAT1 negatively regulates miR‑181a‑5p to promote endometrial carcinoma cell proliferation and migration

Authors:
- Jing Yu
- Lijuan Jiang
- Yutao Gao
- Qijian Sun
- Beibei Liu
- Yong Hu
- Xuesong Han
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Affiliations: Department of Gynecology, The Third Affiliated Hospital of Kunming Medical University and Cancer Hospital of Yunnan Province, Kunming, Yunnan 650118, P.R. China, Department of Scientific Research and Education, The First Affiliated Hospital of Yunnan University of Traditional Chinese Medicine, Kunming, Yunnan 650200, P.R. China, Department of Gynecology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, P.R. China
Published online on: March 20, 2019 https://doi.org/10.3892/etm.2019.7422
Pages: 4259-4266

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Abstract

Long non‑coding RNAs (lncRNAs) are identified as vital modulators in a number of biological processes, including tumorigenesis. However, the role of lncRNAs in endometrial carcinoma (EC) remains unknown. In the current study, the expression patterns, biological roles and functional mechanism of the lncRNA colon cancer associated transcript 1 (CCAT1) was examined in EC. The expression level of CCAT1 was significantly upregulated in EC tissue samples compared with matched adjacent healthy tissue samples from patients with endometrial cancer. Similarly, CCAT1 was significantly upregulated in several EC cell lines (KLE, Ishiwaka and HEC‑1‑A), compared with the normal human endometrial stromal cell line T‑HESC. Cell counting kit‑8 and Transwell migration assays demonstrated that CCAT1 knockdown significantly decreased EC cell proliferation and migration. In addition, CCAT1 was confirmed as a target gene of miR‑181a‑5p in EC. Overexpression of miR‑181a‑5p significantly decreased CCAT1 expression in EC cells, whilst knockdown of CCAT1 significantly increased miR‑181a‑5p expression in EC cells. Furthermore, miR‑181a‑5p expression was significantly downregulated in EC tissue samples compared with matched adjacent healthy tissue samples from patients with endometrial cancer. Similarly, miR‑181a‑5p expression was significantly downregulated in several EC cell lines (KLE, Ishiwaka and HEC‑1‑A), compared with normal human endometrial stromal cell line T‑HESC. In addition, rescue experiments demonstrated that inhibition of miR‑181a‑5p significantly reversed the effect of CCAT1 knockdown on EC cell proliferation and migration. The results suggest that CCAT1 promotes EC progression by acting as a molecular sponge of miR‑181a‑5p.

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1	Felix AS, Scott McMeekin D, Mutch D, Walker JL, Creasman WT, Cohn DE, Ali S, Moore RG, Downs LS, Ioffe OB, et al: Associations between etiologic factors and mortality after endometrial cancer diagnosis: The NRG Oncology/Gynecologic Oncology Group 210 trial. Gynecol Oncol. 139:70–76. 2015. View Article : Google Scholar : PubMed/NCBI
2	Morice P, Leary A, Creutzberg C, Abu-Rustum N and Darai E: Endometrial cancer. Lancet. 387:1094–1108. 2016. View Article : Google Scholar : PubMed/NCBI
3	Cui Z, An X, Li J, Liu Q and Liu W: LncRNA MIR22HG negatively regulates miR-141-3p to enhance DAPK1 expression and inhibits endometrial carcinoma cells proliferation. Biomed Pharmacother. 104:223–228. 2018. View Article : Google Scholar : PubMed/NCBI
4	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 : PubMed/NCBI
5	Lin Z, Zhou Z, Guo H, He Y, Pang X, Zhang X, Liu Y, Ao X, Li P, Wang J, et al: Long noncoding RNA gastric cancer-related lncRNA1 mediates gastric malignancy through miRNA-885-3p and cyclin-dependent kinase 4. Cell Death Dis. 9:6072018. View Article : Google Scholar : PubMed/NCBI
6	Quinn JJ and Chang HY: Unique features of long non-coding RNA biogenesis and function. Nat Rev Genet. 17:47–62. 2016. View Article : Google Scholar : PubMed/NCBI
7	Zhu P, Wang Y, Wu J, Huang G, Liu B, Ye B, Du Y, Gao G, Tian Y, He L and Fan Z: LncBRM initiates YAP1 signalling activation to drive self-renewal of liver cancer stem cells. Nat Commun. 7:136082016. View Article : Google Scholar : PubMed/NCBI
8	Zhou W, Wang L, Miao Y and Xing R: Novel long noncoding RNA GACAT3 promotes colorectal cancer cell proliferation, invasion and migration through miR-149. Onco Targets Ther. 11:1543–1552. 2018. View Article : Google Scholar : PubMed/NCBI
9	Cen C, Li J, Liu J, Yang M, Zhang T, Zuo Y, Lin C and Li X: Long noncoding RNA LINC01510 promotes the growth of colorectal cancer cells by modulating MET expression. Cancer Cell Int. 18:452018. View Article : Google Scholar : PubMed/NCBI
10	Zhang K, Zhao Z, Yu J, Chen W, Xu Q and Chen L: LncRNA FLVCR1-AS1 acts as miR-513c sponge to modulate cancer cell proliferation, migration and invasion in hepatocellular carcinoma. J Cell Biochem. 119:6045–6056. 2018. View Article : Google Scholar : PubMed/NCBI
11	Guo E, Liang C, He X, Song G, Liu H, Lv Z, Guan J, Yang D and Zheng J: Long Noncoding RNA LINC00958 Accelerates Gliomagenesis Through Regulating miR-203/CDK2. DNA Cell Biol. 37:465–472. 2018. View Article : Google Scholar : PubMed/NCBI
12	Yang T, Zhai H, Yan R, Zhou Z, Gao L and Wang L: lncRNA CCAT1 promotes cell proliferation, migration and invasion by down-regulation of miR-143 in FTC-133 thyroid carcinoma cell line. Braz J Med Biol Res. 51:e70462018. View Article : Google Scholar : PubMed/NCBI
13	Li Y, Jing F, Ding Y, He Q, Zhong Y and Fan C: Long noncoding RNA CCAT1 polymorphisms are associated with the risk of colorectal cancer. Cancer Genet. 222-223:13–19. 2018. View Article : Google Scholar : PubMed/NCBI
14	Lai XJ and Cheng HF: LncRNA colon cancer-associated transcript 1 (CCAT1) promotes proliferation and metastasis of ovarian cancer via miR-1290. Eur Rev Med Pharmacol Sci. 22:322–328. 2018.PubMed/NCBI
15	Li Y, Zhu G, Ma Y and Qu H: LncRNA CCAT1 contributes to the growth and invasion of gastric cancer via targeting miR-219-1. J Cell Biochem. 2017.(Epub ahead of print). View Article : Google Scholar
16	Chen L, Hu N, Wang C, Zhao H and Gu Y: Long non-coding RNA CCAT1 promotes multiple myeloma progression by acting as a molecular sponge of miR-181a-5p to modulate HOXA1 expression. Cell Cycle. 17:319–329. 2018. View Article : Google Scholar : PubMed/NCBI
17	Lai Y, Chen Y, Lin Y and Ye L: Down-regulation of LncRNA CCAT1 enhances radiosensitivity via regulating miR-148b in breast cancer. Cell Biol Int. 42:227–236. 2018. View Article : Google Scholar : PubMed/NCBI
18	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
19	Korhan P, Erdal E and Atabey N: MiR-181a-5p is downregulated in hepatocellular carcinoma and suppresses motility, invasion and branching-morphogenesis by directly targeting c-Met. Biochem Biophys Res Commun. 450:1304–1312. 2014. View Article : Google Scholar : PubMed/NCBI
20	Prensner JR and Chinnaiyan AM: The emergence of lncRNAs in cancer biology. Cancer Discov. 1:391–407. 2011. View Article : Google Scholar : PubMed/NCBI
21	Zhang MH, Yang Y, Zhao Y, Wei HB, Ma YQ, Yang CJ, Zhang XJ and Sun YL: LncRNA DQ786243 expression as a biomarker for assessing prognosis in patients with gastric cancer. Eur Rev Med Pharmacol Sci. 22:2304–2309. 2018.PubMed/NCBI
22	Wang YH, Liu YH, Ji YJ, Wei Q and Gao TB: Upregulation of long non-coding RNA HNF1A-AS1 is associated with poor prognosis in urothelial carcinoma of the bladder. Eur Rev Med Pharmacol Sci. 22:2261–2265. 2018.PubMed/NCBI
23	Yang H, Wang S, Kang YJ, Wang C, Xu Y, Zhang Y and Jiang Z: Long non-coding RNA SNHG1 predicts a poor prognosis and promotes colon cancer tumorigenesis. Oncol Rep. 40:261–271. 2018.PubMed/NCBI
24	Li W, Dou Z, We S, Zhu Z, Pan D, Jia Z, Liu H, Wang X and Yu G: Long noncoding RNA BDNF-AS is associated with clinical outcomes and has functional role in human prostate cancer. Biomed Pharmacother. 102:1105–1110. 2018. View Article : Google Scholar : PubMed/NCBI
25	Xiao Z, Qu Z, Chen Z, Fang Z, Zhou K, Huang Z, Guo X and Zhang Y: LncRNA HOTAIR is a prognostic biomarker for the proliferation and chemoresistance of colorectal cancer via MiR-203a-3p-mediated Wnt/β-catenin signaling pathway. Cell Physiol Biochem. 46:1275–1285. 2018. View Article : Google Scholar : PubMed/NCBI
26	Cao Y, Shi H, Ren F, Jia Y and Zhang R: Long non-coding RNA CCAT1 promotes metastasis and poor prognosis in epithelial ovarian cancer. Exp Cell Res. 359:185–194. 2017. View Article : Google Scholar : PubMed/NCBI
27	Zhang Y and Hu H: Long non-coding RNA CCAT1/miR-218/ZFX axis modulates the progression of laryngeal squamous cell cancer. Tumour Biol. 39:10104283176994172017.PubMed/NCBI
28	Zhao J and Cheng L: Long non-coding RNA CCAT1/miR-148a axis promotes osteosarcoma proliferation and migration through regulating PIK3IP1. Acta Biochim Biophys Sin (Shanghai). 49:503–512. 2017. View Article : Google Scholar : PubMed/NCBI
29	Arunkumar G, Murugan AK, Prasanna Srinivasa Rao H, Subbiah S, Rajaraman R and Munirajan AK: Long non-coding RNA CCAT1 is overexpressed in oral squamous cell carcinomas and predicts poor prognosis. Biomed Rep. 6:455–462. 2017. View Article : Google Scholar : PubMed/NCBI
30	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
31	Xu D, Yu J, Gao G, Lu G, Zhang Y and Ma P: LncRNA DANCR functions as a competing endogenous RNA to regulate RAB1A expression by sponging miR-634 in glioma. Biosci Rep. 38(pii): BSR201716642018. View Article : Google Scholar : PubMed/NCBI
32	Zhu J, Shi H, Liu H, Wang X and Li F: Long non-coding RNA TUG1 promotes cervical cancer progression by regulating the miR-138-5p-SIRT1 axis. Oncotarget. 8:65253–65264. 2017.PubMed/NCBI
33	Chen Z, Wu J, Huang W, Peng J, Ye J, Yang L, Yuan Y, Chen C, Zhang C, Cai S, et al: Long non-coding RNA RP11-789C1.1 suppresses epithelial to mesenchymal transition in gastric cancer through the RP11-789C1.1/MiR-5003/E-cadherin axis. Cell Physiol Biochem. 47:2432–2444. 2018. View Article : Google Scholar : PubMed/NCBI
34	Feng L, Shi L, Lu YF, Wang B, Tang T, Fu WM, He W, Li G and Zhang JF: Linc-ROR promotes osteogenic differentiation of mesenchymal stem cells by functioning as a competing endogenous RNA for miR-138 and miR-145. Mol Ther Nucleic Acids. 11:345–353. 2018. View Article : Google Scholar : PubMed/NCBI
35	Li S, Yang J, Xia Y, Fan Q and Yang KP: Long Noncoding RNA NEAT1 Promotes proliferation and invasion via targeting miR-181a-5p in non-small cell lung cancer. Oncol Res. 26:289–296. 2018. View Article : Google Scholar : PubMed/NCBI
36	Liu Z, Sun F, Hong Y, Wang B, Tang T, Fu WM, He W, Li G and Zhang JF: MEG2 is regulated by miR-181a-5p and functions as a tumour suppressor gene to suppress the proliferation and migration of gastric cancer cells. Mol Cancer. 16:1332017. View Article : Google Scholar : PubMed/NCBI
37	Yang M, Zhai X, Ge T, Yang C and Lou G: MiR-181a-5p promotes proliferation and invasion and inhibits apoptosis of cervical cancer cells via regulating inositol polyphosphate-5-phosphatase A (INPP5A). Oncol Res. 26:703–712. 2017. View Article : Google Scholar : PubMed/NCBI
38	Yang CH, Zhang XY, Zhou LN, Wan Y, Song LL, Gu WL, Liu R, Ma YN, Meng HR, Tian YL and Zhang Y: LncRNA SNHG8 participates in the development of endometrial carcinoma through regulating c-MET expression by miR-152. Eur Rev Med Pharmacol Sci. 22:1629–1637. 2018.PubMed/NCBI