MicroRNA‑429 acts as a tumor suppressor in colorectal cancer by targeting high mobility group box 3

Tian,Xiangyang; Chang,Jianlan; Zhang,Ningning; Wu,Shouxin; Liu,Huimin; Yu,Junyan

doi:10.3892/ol.2021.12511

MicroRNA‑429 acts as a tumor suppressor in colorectal cancer by targeting high mobility group box 3

Authors:
- Xiangyang Tian
- Jianlan Chang
- Ningning Zhang
- Shouxin Wu
- Huimin Liu
- Junyan Yu
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Affiliations: Department of Oncology, Heping Hospital, Changzhi Medical College, Changzhi, Shanxi 046000, P.R. China, Biotecan Medical Diagnostics Co., Ltd., Zhangjiang Center for Translational Medicine, Shanghai 201203, P.R. China
Published online on: February 3, 2021 https://doi.org/10.3892/ol.2021.12511
Article Number: 250
Copyright: © Tian 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 one of the most common solid tumors worldwide and has an extremely poor prognosis. MicroRNA‑429 (miR‑429) has been reported to participate in the progression of CRC. However, the pathological mechanisms require further investigation. The aim of the present study was to investigate the association between miR‑429 and high mobility group box 3 (HMGB3) in CRC and the associated mechanism. The mRNA expression levels of miR‑429 and HMGB3 in 65 paired CRC and adjacent tissues were examined by reverse transcription‑quantitative PCR. Furthermore, a dual‑luciferase reporter assay was performed to identify the association between miR‑429 and HMGB3. Finally, the effects of miR‑429 and HMGB3 on the proliferation and apoptosis of CRC cells were detected. As a result, it was identified that miR‑429 expression was downregulated and HMGB3 expression was upregulated in CRC tissues compared with in adjacent non‑cancer tissues, and the expression levels of miR‑429 were negatively associated with those of HMGB3. Notably, HMGB3 was demonstrated to be a direct target of miR‑429 by dual‑luciferase reporter assay. Furthermore, transfection with a miR‑429 mimic significantly inhibited HMGB3 expression and led to decreased proliferation and increased apoptosis of CRC cells. On the other hand, transient overexpression of HMGB3 partially inhibited the antitumor effects of miR‑429. To the best of our knowledge, the present study demonstrated for the first time that miR‑429 regulated the proliferation and apoptosis of CRC cells via HMGB3, suggesting a specific tumor suppressive function of the miR‑429/HMGB3 signaling pathway in CRC.

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1	Gormley JA, Hegarty SM, O'Grady A, Stevenson MR, Burden RE, Barrett HL, Scott CJ, Johnston JA, Wilson RH, Kay EW, et al: The role of cathepsin S as a marker of prognosis and predictor of chemotherapy benefit in adjuvant CRC: A pilot study. Br J Cancer. 105:1487–1494. 2011. View Article : Google Scholar : PubMed/NCBI
2	Nikolouzakis TK, Vassilopoulou L, Fragkiadaki P, Mariolis Sapsakos T, Papadakis GZ, Spandidos DA, Tsatsakis AM and Tsiaoussis J: Improving diagnosis, prognosis and prediction by using biomarkers in CRC patients (Review). Oncol Rep. 39:2455–2472. 2018.PubMed/NCBI
3	Wu J, Wang F, Liu X, Zhang T, Liu F, Ge X, Mao Y and Hua D: Correlation of IDH1 and B7H3 expression with prognosis of CRC patients. Eur J Surg Oncol. 44:1254–1260. 2018. View Article : Google Scholar : PubMed/NCBI
4	Costa DF and Torchilin VP: Micelle-like nanoparticles as siRNA and miRNA carriers for cancer therapy. Biomed Microdevices. 20:592018. View Article : Google Scholar : PubMed/NCBI
5	Xu B, Liu J, Xiang X, Liu S, Zhong P, Xie F, Mou T and Lai L: Expression of miRNA-143 in pancreatic cancer and its clinical significance. Cancer Biother Radiopharm. 33:373–379. 2018. View Article : Google Scholar : PubMed/NCBI
6	Chen Y, Zhao J, Luo Y, Wang Y and Jiang Y: Downregulated expression of miRNA-149 promotes apoptosis in side population cells sorted from the TSU prostate cancer cell line. Oncol Rep. 36:2587–2600. 2016. View Article : Google Scholar : PubMed/NCBI
7	Ju H, Tan JY, Cao B, Song MQ and Tian ZB: Effects of miR-223 on colorectal cancer cell proliferation and apoptosis through regulating FoxO3a/BIM. Eur Rev Med Pharmacol Sci. 22:3771–3778. 2018.PubMed/NCBI
8	Su M, Qin B, Liu F, Chen Y and Zhang R: miR-885-5p upregulation promotes colorectal cancer cell proliferation and migration by targeting suppressor of cytokine signaling. Oncol Lett. 16:65–72. 2018.PubMed/NCBI
9	Li L, Zhang X, Yi Z, Liang X, Yin W and Li S: MiR-503 promotes the migration and invasion of colorectal cancer cells by regulating PDCD4. J BUON. 23:579–586. 2018.PubMed/NCBI
10	Afshar S, Najafi R, Sedighi Pashaki A, Sharifi M, Nikzad S, Gholami MH, Khoshghadam A, Amini R, Karimi J and Saidijam M: MiR-185 enhances radiosensitivity of colorectal cancer cells by targeting IGF1R and IGF2. Biomed Pharmacother. 106:763–769. 2018. View Article : Google Scholar : PubMed/NCBI
11	Tian X, Wei Z, Wang J, Liu P, Qin Y and Zhong M: MicroRNA-429 inhibits the migration and invasion of colon cancer cells by targeting PAK6/cofilin signaling. Oncol Rep. 34:707–714. 2015. View Article : Google Scholar : PubMed/NCBI
12	Petit A, Ragu C, Della-Valle V, Mozziconacci MJ, Lafage-Pochitaloff M, Soler G, Schluth C, Radford I, Ottolenghi C, Bernard OA, et al: NUP98-HMGB3: A novel oncogenic fusion. Leukemia. 24:654–658. 2010. View Article : Google Scholar : PubMed/NCBI
13	Guo S, Wang Y, Gao Y, Zhang Y, Chen M, Xu M, Hu L, Jing Y, Jing F, Li C, et al: Knockdown of high mobility group-box 3 (HMGB3) expression inhibits proliferation, reduces migration, and affects chemosensitivity in gastric cancer cells. Med Sci Monit. 22:3951–3960. 2016. View Article : Google Scholar : PubMed/NCBI
14	Li M, Cai Y, Zhao H, Xu Z, Sun Q, Luo M, Gu L, Meng M, Han X and Sun H: Overexpression of HMGB3 protein promotes cell proliferation, migration and is associated with poor prognosis in urinary bladder cancer patients. Tumour Biol. 36:4785–4792. 2015. View Article : Google Scholar : PubMed/NCBI
15	Yamada Y, Nishikawa R, Kato M, Okato A, Arai T, Kojima S, Yamazaki K, Naya Y, Ichikawa T and Seki N: Regulation of HMGB3 by antitumor miR-205-5p inhibits cancer cell aggressiveness and is involved in prostate cancer pathogenesis. J Hum Genet. 63:195–205. 2018. View Article : Google Scholar : PubMed/NCBI
16	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
17	Han Y, Zhao Q, Zhou J and Shi R: miR-429 mediates tumor growth and metastasis in colorectal cancer. Am J Cancer Res. 7:218–233. 2017.PubMed/NCBI
18	Sun Y, Shen S, Liu X, Tang H, Wang Z, Yu Z, Li X and Wu M: MiR-429 inhibits cells growth and invasion and regulates EMT-related marker genes by targeting Onecut2 in colorectal carcinoma. Mol Cell Biochem. 390:19–30. 2014. View Article : Google Scholar : PubMed/NCBI
19	Li L, Huang J, Ju Z, Li Q, Wang C, Qi C, Zhang Y, Hou Q, Hang S and Zhong J: Multiple promoters and targeted microRNAs direct the expressions of HMGB3 gene transcripts in dairy cattle. Anim Genet. 44:241–250. 2013. View Article : Google Scholar : PubMed/NCBI
20	Song N, Liu B, Wu JL, Zhang RF, Duan L, He WS and Zhang CM: Prognostic value of HMGB3 expression in patients with non-small cell lung cancer. Tumour Biol. 34:2599–2603. 2013. View Article : Google Scholar : PubMed/NCBI
21	Elgamal OA, Park JK, Gusev Y, Azevedo-Pouly AC, Jiang J, Roopra A and Schmittgen TD: Tumor suppressive function of mir-205 in breast cancer is linked to HMGB3 regulation. PLoS One. 8:e764022013. View Article : Google Scholar : PubMed/NCBI
22	Gao J, Zou Z, Gao J, Zhang H, Lin Z, Zhang Y, Luo X, Liu C, Xie J and Cai C: Increased expression of HMGB3: A novel independent prognostic marker of worse outcome in patients with esophageal squamous cell carcinoma. Int J Clin Exp Pathol. 8:345–352. 2015.PubMed/NCBI
23	Gong Y, Cao Y, Song L, Zhou J, Wang C and Wu B: HMGB3 characterization in gastric cancer. Genet Mol Res. 12:6032–6039. 2013. View Article : Google Scholar : PubMed/NCBI
24	Zhang Z, Chang Y, Zhang J, Lu Y, Zheng L, Hu Y, Zhang F and Li X, Zhang W and Li X: HMGB3 promotes growth and migration in colorectal cancer by regulating WNT/β-catenin pathway. PLoS One. 12:e01797412017. View Article : Google Scholar : PubMed/NCBI