Long non‑coding RNA SNHG12 regulates cell proliferation, invasion and migration in endometrial cancer by targeting miR‑4429

Cai,Pengyu; Wu,Mingxiu; Zhang,Bin; Wu,Shuyi; Wei,Haiyun; Wei,Li

doi:10.3892/mmr.2020.11370

Long non‑coding RNA SNHG12 regulates cell proliferation, invasion and migration in endometrial cancer by targeting miR‑4429

Authors:
- Pengyu Cai
- Mingxiu Wu
- Bin Zhang
- Shuyi Wu
- Haiyun Wei
- Li Wei
View Affiliations

Affiliations: Department of Obstetrics and Gynecology, Dongguan People's Hospital, Dongguan, Guangdong 523000, P.R. China
Published online on: July 28, 2020 https://doi.org/10.3892/mmr.2020.11370
Pages: 2842-2850
Copyright: © Cai et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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 non‑coding RNA small nucleolar RNA host gene 12 (SNHG12) has been demonstrated to be oncogenic. The aim of the present study was to examine the effects of SNHG12 on the progression of endometrial cancer (EC). The expression levels of SNHG12 and microRNA (miR)‑4429 were assessed in EC cell lines by reverse transcription‑quantitative PCR. Plasmids, including SNHG12 short hairpin RNAs (shRNAs), shRNA negative control (NC), SNHG12 overexpression (OV), OV‑NC, miR‑4429 mimic and mimic‑NC, were transfected into RL95‑2 cells. Post‑transfection, Cell Counting Kit‑8, Transwell Matrigel and wound‑healing assays were performed to assess cell proliferation, invasion and migration, respectively. Cell cycle phase distribution was assessed by flow cytometry. The protein expression levels of matrix metalloproteinase (MMP)2 and MMP9 were detected by western blotting. miR‑4429 target genes were predicted by bioinformatics analysis using target prediction online tools; the findings of this analysis were verified using a dual‑luciferase reporter system. Identified as a target of miR‑4429, SNHG12 was overexpressed in EC cell lines with decreased expression of miR‑4429. Further experiments demonstrated that SNHG12 silencing and overexpression of miR‑4429 markedly suppressed proliferation, migration and invasion of RL95‑2 cells, arrested cells in the G1 phase, and markedly downregulated the expression of MMP2 and MMP9. The opposite effects were observed in miR‑4429 mimic‑transfected RL95‑2 cells after SNHG12 was overexpressed. The findings of the present study established the role of SNHG12 and miR‑4429 in EC. Therefore, targeting the SNHG12/miR‑4429 axis could serve as a potential future therapeutic target for treatment of EC.

View Figures

View References

1	Brooks RA, Fleming GF, Lastra RR, Lee NK, Moroney JW, Son CH, Tatebe K and Veneris JL: Current recommendations and recent progress in endometrial cancer. CA Cancer J Clin. 69:2842–279. 2019.
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	Van Nyen T, Moiola CP, Colas E, Annibali D and Amant F: Modeling endometrial cancer: Past, present, and future. Int J Mol Sci. 19:23482018. View Article : Google Scholar
4	Kahlert C and Kalluri R: Exosomes in tumor microenvironment influence cancer progression and metastasis. J Mol Med (Berl). 91:431–437. 2013. View Article : Google Scholar : PubMed/NCBI
5	Zhou M, Zhong L, Xu W, Sun Y, Zhang Z, Zhao H, Yang L and Sun J: Discovery of potential prognostic long non-coding RNA biomarkers for predicting the risk of tumor recurrence of breast cancer patients. Sci Rep. 6:310382016. View Article : Google Scholar : PubMed/NCBI
6	Zhou M, Xu W, Yue X, Zhao H, Wang Z, Shi H, Cheng L and Sun J: Relapse-related long non-coding RNA signature to improve prognosis prediction of lung adenocarcinoma. Oncotarget. 7:29720–29738. 2016. View Article : Google Scholar : PubMed/NCBI
7	Zhou M, Sun Y, Sun Y, Xu W, Zhang Z, Zhao H, Zhong Z and Sun J: Comprehensive analysis of lncRNA expression profiles reveals a novel lncRNA signature to discriminate nonequivalent outcomes in patients with ovarian cancer. Oncotarget. 7:32433–32448. 2016. View Article : Google Scholar : PubMed/NCBI
8	Li J, Xue W, Lv J, Han P, Liu Y and Cui B: Identification of potential long non-coding RNA biomarkers associated with the progression of colon cancer. Oncotarget. 8:75834–75843. 2017. View Article : Google Scholar : PubMed/NCBI
9	Zhang XH, Hu P, Xie YQ, Kang YJ and Li M: lncRNA HOTAIR promotes endometrial carcinoma cells proliferation by binding to PTEN via activating PI3k/Akt signaling pathway. Mol Cell Biol. 39:e00251–e00219. 2019. View Article : Google Scholar : PubMed/NCBI
10	Liu ZB, Tang C, Jin X, Liu SH and Pi W: Increased expression of lncRNA SNHG12 predicts a poor prognosis of nasopharyngeal carcinoma and regulates cell proliferation and metastasis by modulating notch signal pathway. Cancer Biomark. 23:603–613. 2018. View Article : Google Scholar : PubMed/NCBI
11	Feng X, Dong X, Wu D, Zhao H, Xu C and Li H: Long noncoding RNA small nucleolar RNA host gene 12 promotes papillary thyroid carcinoma cell growth and invasion by targeting miR-16-5p. Histol Histopathol. 35:217–224. 2020.PubMed/NCBI
12	Liu Y, Zhou J, Wang S, Song Y, Zhou J and Ren F: Long non-coding RNA SNHG12 promotes proliferation and invasion of colorectal cancer cells by acting as a molecular sponge of microRNA-16. Exp Ther Med. 18:1212–1220. 2019.PubMed/NCBI
13	Sun D and Fan XH: LncRNA SNHG12 accelerates the progression of ovarian cancer via absorbing miRNA-129 to upregulate SOX4. Eur Rev Med Pharmacol Sci. 23:2345–2352. 2019.PubMed/NCBI
14	Jin XJ, Chen XJ, Zhang ZF, Hu WS, Ou RY, Li S, Xue JS, Chen LL, Hu Y and Zhu H: Long noncoding RNA SNHG12 promotes the progression of cervical cancer via modulating miR-125b/STAT3 axis. J Cell Physiol. 234:6624–6632. 2019. View Article : Google Scholar : PubMed/NCBI
15	Liu X, Chen R and Liu L: SP1-DLEU1-miR-4429 feedback loop promotes cell proliferative and anti-apoptotic abilities in human glioblastoma. Biosci Rep. 39:BSR201909942019. View Article : Google Scholar : PubMed/NCBI
16	Wu WJ, Yin H, Hu JJ and Wei XZ: Long noncoding RNA LINC00313 modulates papillary thyroid cancer tumorigenesis via sponging miR-4429. Neoplasma. 65:933–942. 2018. View Article : Google Scholar : PubMed/NCBI
17	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
18	Braun MM, Overbeek-Wager EA and Grumbo RJ: Diagnosis and management of endometrial cancer. Am Fam Physician. 93:468–474. 2016.PubMed/NCBI
19	Lee YC, Lheureux S and Oza AM: Treatment strategies for endometrial cancer: Current practice and perspective. Curr Opin Obstet Gynecol. 29:47–58. 2017. View Article : Google Scholar : PubMed/NCBI
20	Njoku K, Chiasserini D, Whetton AD and Crosbie EJ: Proteomic biomarkers for the detection of endometrial cancer. Cancers (Basel). 11:15722019. View Article : Google Scholar
21	Khandelwal A, Malhotra A, Jain M, Vasquez KM and Jain A: The emerging role of long non-coding RNA in gallbladder cancer pathogenesis. Biochimie. 132:152–160. 2017. View Article : Google Scholar : PubMed/NCBI
22	Malhotra A, Sharma U, Puhan S, Chandra Bandari N, Kharb A, Arifa PP, Thakur L, Prakash H, Vasquez KM and Jain A: Stabilization of miRNAs in esophageal cancer contributes to radioresistance and limits efficacy of therapy. Biochimie. 156:148–157. 2019. View Article : Google Scholar : PubMed/NCBI
23	Tamang S, Acharya V, Roy D, Sharma R, Aryaa A, Sharma U, Khandelwal A, Prakash H, Vasquez KM and Jain A: SNHG12: An LncRNA as a potential therapeutic target and biomarker for human cancer. Front Oncol. 9:9012019. View Article : Google Scholar : PubMed/NCBI
24	Lan T, Ma W, Hong Z, Wu L, Chen X and Yuan Y: Long non-coding RNA small nucleolar RNA host gene 12 (SNHG12) promotes tumorigenesis and metastasis by targeting miR-199a/b-5p in hepatocellular carcinoma. J Exp Clin Cancer Res. 36:112017. View Article : Google Scholar : PubMed/NCBI
25	Chen P, Hu MD, Deng XF and Li B: Genistein reinforces the inhibitory effect of cisplatin on liver cancer recurrence and metastasis after curative hepatectomy. Asian Pac J Cancer Prev. 14:759–764. 2013. View Article : Google Scholar : PubMed/NCBI
26	Tan JY and Marques AC: miRNA-mediated crosstalk between transcripts: The missing ‘linc’? Bioessays. 38:295–301. 2016. View Article : Google Scholar : PubMed/NCBI
27	Liu X, Zheng J, Xue Y, Qu C, Chen J, Wang Z, Li Z, Zhang L and Liu Y: Inhibition of TDP43-mediated SNHG12-miR-195-SOX5 feedback loop impeded malignant biological behaviors of glioma cells. Mol Ther Nucleic Acids. 10:142–158. 2018. View Article : Google Scholar : PubMed/NCBI
28	Sun Y, Liu J, Chu L, Yang W, Liu H, Li C and Yang J: Long noncoding RNA SNHG12 facilitates the tumorigenesis of glioma through miR-101-3p/FOXP1 axis. Gene. 676:315–321. 2018. View Article : Google Scholar : PubMed/NCBI
29	Sun H, Fan G, Deng C and Wu L: miR-4429 sensitized cervical cancer cells to irradiation by targeting RAD51. J Cell Physiol. 235:185–193. 2020. View Article : Google Scholar : PubMed/NCBI
30	Pan H, Hong Y, Yu B, Li L and Zhang X: miR-4429 inhibits tumor progression and epithelial-mesenchymal transition via targeting CDK6 in clear cell renal cell carcinoma. Cancer Biother Radiopharm. 34:334–341. 2019. View Article : Google Scholar : PubMed/NCBI