MEX3A knockdown inhibits the tumorigenesis of colorectal cancer via modulating CDK2 expression

Zhou,Xin; Li,Shaojie; Ma,Tiexiang; Zeng,Jian; Li,Huanyu; Liu,Xiang; Li,Feng; Jiang,Bin; Zhao,Ming; Liu,Zhuo; Qin,Yiyu

doi:10.3892/etm.2021.10778

MEX3A knockdown inhibits the tumorigenesis of colorectal cancer via modulating CDK2 expression

Authors:
- Xin Zhou
- Shaojie Li
- Tiexiang Ma
- Jian Zeng
- Huanyu Li
- Xiang Liu
- Feng Li
- Bin Jiang
- Ming Zhao
- Zhuo Liu
- Yiyu Qin
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Affiliations: Department of General Surgery, Xiangtan Central Hospital, Xiangtan, Hunan 411100, P.R. China, Clinical Medical College, Follow-up Research Center, Jiangsu Vocational College of Medicine, Yancheng, Jiangsu 224005, P.R. China
Published online on: September 22, 2021 https://doi.org/10.3892/etm.2021.10778
Article Number: 1343
Copyright: © Zhou et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Colorectal cancer (CRC) is a malignant tumor of the gastrointestinal tract and a leading cause of cancer‑associated mortality worldwide. Mex‑3 RNA binding family member A (MEX3A) promotes the progression of multiple types of cancer, including ovarian and cervical cancer. However, to the best of our knowledge, the role of MEX3A in CRC is not completely understood. Therefore, the present study aimed to investigate the function of MEX3A in CRC. The mRNA and protein expression levels of MEX3A in CRC cells were analyzed using reverse transcription‑quantitative PCR and western blotting, respectively. Cell Counting Kit‑8 assays were used to measure cell viability. Cell apoptosis and cell cycle distribution were detected via flow cytometry, and CRC cell invasion was analyzed by performing Transwell assays. Moreover, the mitochondrial membrane potential in CRC cells was measured via JC‑1 staining. The results of the present study revealed that the expression levels of MEX3A were upregulated in CRC tissues compared with adjacent healthy tissues. MEX3A knockdown notably inhibited CRC cell viability, and induced apoptosis and mitochondrial injury. In addition, MEX3A knockdown markedly induced G1 phase cell cycle arrest in CRC cells via downregulating CDK2 expression. In conclusion, the findings of the present study suggested that MEX3A knockdown may inhibit the tumorigenesis of CRC cells by regulating CDK2 expression. Therefore, MEX3A may serve as a novel target for CRC treatment.

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1	Parine NR, Azzam NA, Shaik J, Aljebreen AM, Alharbi O, Almadi MA, Alanazi M and Khan Z: Genetic variants in the WNT signaling pathway are protectively associated with colorectal cancer in a Saudi population. Saudi J Biol Sci. 26:286–293. 2019.PubMed/NCBI View Article : Google Scholar
2	Feroldi F, Verlaan M, Knaus H, Davidoiu V, Vugts DJ, van Dongen GA, Molthoff CF and de Boer JF: High resolution combined molecular and structural optical imaging of colorectal cancer in a xenograft mouse model. Biomed Opt Express. 9:6186–6204. 2018.PubMed/NCBI View Article : Google Scholar
3	Gala de Pablo J, Armistead FJ, Peyman SA, Bonthron D, Lones M, Smith S and Evans SD: Biochemical fingerprint of colorectal cancer cell lines using label-free live single-cell Raman spectroscopy. J Raman Spectrosc. 49:1323–1332. 2018.PubMed/NCBI View Article : Google Scholar
4	Panzeri V, Manni I, Capone A, Naro C, Sacconi A, Di Agostino S, de Latouliere L, Montori A, Pilozzi E, Piaggio G, et al: The RNA-binding protein MEX3A is a prognostic factor and regulator of resistance to gemcitabine in pancreatic ductal adenocarcinoma. Mol Oncol. 15:579–595. 2021.PubMed/NCBI View Article : Google Scholar
5	Naef V, De Sarlo M, Testa G, Corsinovi D, Azzarelli R, Borello U and Ori M: The stemness gene Mex3A is a key regulator of neuroblast proliferation during neurogenesis. Front Cell Dev Biol. 8(549533)2020.PubMed/NCBI View Article : Google Scholar
6	Liang J, Li H, Han J, Jiang J, Wang J, Li Y, Feng Z, Zhao R, Sun Z, Lv B, et al: Mex3a interacts with LAMA2 to promote lung adenocarcinoma metastasis via PI3K/AKT pathway. Cell Death Dis. 11(614)2020.PubMed/NCBI View Article : Google Scholar
7	Jiang S, Meng L, Chen X, Liu H, Zhang J, Chen F, Zheng J, Liu H, Wang F, Hu J, et al: MEX3A promotes triple negative breast cancer proliferation and migration via the PI3K/AKT signaling pathway. Exp Cell Res. 395(112191)2020.PubMed/NCBI View Article : Google Scholar
8	Wang X, Shan YQ, Tan QQ, Tan CL, Zhang H, Liu JH, Ke NW, Chen YH and Liu XB: MEX3A knockdown inhibits the development of pancreatic ductal adenocarcinoma. Cancer Cell Int. 20(63)2020.PubMed/NCBI View Article : Google Scholar
9	Bufalieri F, Caimano M, Lospinoso Severini L, Basili I, Paglia F, Sampirisi L, Loricchio E, Petroni M, Canettieri G, Santoro A, et al: The RNA-binding ubiquitin ligase MEX3A affects glioblastoma tumorigenesis by inducing ubiquitylation and degradation of RIG-I. Cancers (Basel). 12(12)2020.PubMed/NCBI View Article : Google Scholar
10	Yang D, Jiao Y, Li Y and Fang X: Clinical characteristics and prognostic value of MEX3A mRNA in liver cancer. PeerJ. 8(e8252)2020.PubMed/NCBI View Article : Google Scholar
11	Jiang H, Zhang X, Luo J, Dong C, Xue J, Wei W, Chen J, Zhou J, Gao Y and Yang C: Knockdown of hMex-3A by small RNA interference suppresses cell proliferation and migration in human gastric cancer cells. Mol Med Rep. 6:575–580. 2012.PubMed/NCBI View Article : Google Scholar
12	Yang C, Zhan H, Zhao Y, Wu Y, Li L and Wang H: MEX3A contributes to development and progression of glioma through regulating cell proliferation and cell migration and targeting CCL2. Cell Death Dis. 12(14)2021.PubMed/NCBI View Article : Google Scholar
13	Jin X, Ge LP, Li DQ, Shao ZM, Di GH, Xu XE and Jiang YZ: LncRNA TROJAN promotes proliferation and resistance to CDK4/6 inhibitor via CDK2 transcriptional activation in ER⁺ breast cancer. Mol Cancer. 19(87)2020.PubMed/NCBI View Article : Google Scholar
14	Krepischi ACV, Maschietto M, Ferreira EN, Silva AG, Costa SS, da Cunha IW, Barros BDF, Grundy PE, Rosenberg C and Carraro DM: Genomic imbalances pinpoint potential oncogenes and tumor suppressors in Wilms tumors. Mol Cytogenet. 9(20)2016.PubMed/NCBI View Article : Google Scholar
15	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.PubMed/NCBI View Article : Google Scholar
16	Pereira B, Sousa S, Barros R, Carreto L, Oliveira P, Oliveira C, Chartier NT, Plateroti M, Rouault JP, Freund JN, et al: CDX2 regulation by the RNA-binding protein MEX3A: Impact on intestinal differentiation and stemness. Nucleic Acids Res. 41:3986–3999. 2013.PubMed/NCBI View Article : Google Scholar
17	Li H, Liang J, Wang J, Han J, Li S, Huang K and Liu C: Mex3a promotes oncogenesis through the RAP1/MAPK signaling pathway in colorectal cancer and is inhibited by hsa-miR-6887-3p. Cancer Commun (Lond). 41:472–491. 2021.PubMed/NCBI View Article : Google Scholar
18	Peng W, Li J, Chen R, Gu Q, Yang P, Qian W, Ji D, Wang Q, Zhang Z, Tang J, et al: Upregulated METTL3 promotes metastasis of colorectal Cancer via miR-1246/SPRED2/MAPK signaling pathway. J Exp Clin Cancer Res. 38(393)2019.PubMed/NCBI View Article : Google Scholar
19	He X, Li S, Yu B, Kuang G, Wu Y, Zhang M, He Y, Ou C and Cao P: LINC00467Up-regulation of promotes the tumourigenesis in colorectal cancer. J Cancer. 10:6405–6413. 2019.PubMed/NCBI View Article : Google Scholar
20	Wells N, Quigley J, Pascua J, Pinkowski N, Almaiman L, Brasser SM and Hong MY: Effects of low-to-moderate ethanol consumption on colonic growth and gene expression in young adult and middle-aged male rats. PLoS One. 15(e0243499)2020.PubMed/NCBI View Article : Google Scholar
21	Kumarasamy V, Vail P, Nambiar R, Witkiewicz AK and Knudsen ES: Functional determinants of cell-cycle plasticity and sensitivity to CDK4/6 inhibition. Cancer Res. 81:1347–1360. 2021.PubMed/NCBI View Article : Google Scholar
22	Shih LJ, Wang JY, Jheng JY, Siao AC, Lin YY, Tsuei YW, Kuo YC, Chuu CP and Kao YH: Betel nut arecoline induces different phases of growth arrest between normal and cancerous prostate cells through the reactive oxygen species pathway. Int J Mol Sci. 21(21)2020.PubMed/NCBI View Article : Google Scholar
23	Pandey K, Park N, Park KS, Hur J, Cho YB, Kang M, An HJ, Kim S, Hwang S and Moon YW: Combined CDK2 and CDK4/6 inhibition overcomes palbociclib resistance in breast cancer by enhancing senescence. Cancers (Basel). 12(12)2020.PubMed/NCBI View Article : Google Scholar
24	Qu X, Zhu L, Song L and Liu S: circ_0084927 promotes cervical carcinogenesis by sponging miR-1179 that suppresses CDK2, a cell cycle-related gene. Cancer Cell Int. 20(333)2020.PubMed/NCBI View Article : Google Scholar
25	Zhao Y, He J, Li Y, Xu M, Peng X, Mao J, Xu B and Cui H: PHF14 promotes cell proliferation and migration through the AKT and ERK1/2 pathways in gastric cancer cells. BioMed Res Int. 2020(6507510)2020.PubMed/NCBI View Article : Google Scholar
26	Xu X, Tao R, Sun L and Ji X: Exosome-transferred hsa_circ_0014235 promotes DDP chemoresistance and deteriorates the development of non-small cell lung cancer by mediating the miR-520a-5p/CDK4 pathway. Cancer Cell Int. 20(552)2020.PubMed/NCBI View Article : Google Scholar