miR-196a targeting LRIG3 promotes the proliferation and migration of cervical cancer cells

Yunfen Qiu; Qing Han; Hong Lu; Chunming Shi

doi:10.14715/cmb/2020.66.7.27

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Vol. 66 No. 7: Issue 7

Issue Published : November 9, 2020

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miR-196a targeting LRIG3 promotes the proliferation and migration of cervical cancer cells

https://doi.org/10.14715/cmb/2020.66.7.27

Yunfen Qiu

Department of Gynecology, Nantong Tumor Hospital,Nantong 226001,Jiangsu,China

Qing Han

Department of Gynecology, Nantong Tumor Hospital,Nantong 226001,Jiangsu,China

Hong Lu

Department of Gynecology, Nantong Tumor Hospital,Nantong 226001,Jiangsu,China

Chunming Shi

Department of Gynecology, Nantong Tumor Hospital,Nantong 226001,Jiangsu,China

Corresponding Author(s) : Chunming Shi

gugwe7@163.com

Cellular and Molecular Biology, Vol. 66 No. 7: Issue 7
Article Published : October 31, 2020

Abstract

In recent years, studies have found that miR-RNA plays a role in cell proliferation, differentiation, apoptosis and metabolism. Among them, miR-196a is closely related to cervical cancer. Therefore, this experiment investigates the effect of mir-196a expression on cervical cancer cells and related mechanisms. The expression level of miR-196a in the cervical cancer cell line was assayed with the RT-PCR method, and liposome transfection was used to investigate its up-regulation or down-regulation in cervical cancer cells. The CCK-8 method and flow cytometry were used to measure cervical cancer cell proliferation and apoptosis, while the Transwell assay was used to determine cell migration and invasion of each transfection group. Bioinformatics was used to predict the target gene of miR-196a, which was verified using dual luciferase report experiment and Western blot, and miR-196a was further transfected with si-LRIG3 to detect its reversal effect on miR-196a regulation. Inhibition of the expression of miR-196a significantly reduced the proliferation, migration and invasion of cervical cancer cells, and promoted their apoptosis. Results from dual luciferase assay showed that miR-196a and LRIG3 had direct targeting effects. Cell proliferation, migration and invasion were enhanced by a reduction in the expression level of LRIG3 protein after miR-196a inhibitor cells were transfected with si-LRIG3. The expression of miR-196a is up-regulated in cervical cancer, and it promotes the growth of cervical cancer by its targeting effect on LRIG3 expression, resulting in enhancement of the proliferation, migration and invasion ability of cervical cancer cells, and inhibition of apoptosis.

Keywords

miR-196a Cervical cancer Cell proliferation LRIG3.

Qiu, Y., Han, Q., Lu, H., & Shi, C. (2020). miR-196a targeting LRIG3 promotes the proliferation and migration of cervical cancer cells. Cellular and Molecular Biology, 66(7), 180–185. https://doi.org/10.14715/cmb/2020.66.7.27

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References

Cancer Genome Atlas Research Network. Integrated genomic and molecular characterization of cervical cancer. Nature 2017; 543: 378.
Ludwig N, Leidinger P, Becker K, Backes C, Fehlmann T, Pallasch C, et al. Distribution of miRNA expression across human tissues. Nucleic Acids Res 2016; 44: 3865-3877.
Reddy KB. MicroRNA (miRNA) in cancer. Cancer Cell Int 2015; 15: 38.
Pan Y, Shu X, Sun L, Yu L, Sun L, Yang Z, et al. miR"‘196a"‘5p modulates gastric cancer stem cell characteristics by targeting Smad4. Int J Oncol 2017; 50: 1965-1976.
Chen X, Du P, She J, Cao L, Li Y, Xia H. Loss of ZG16 is regulated by miR-196a and contributes to stemness and progression of colorectal cancer. Oncotarget 2016; 7: 86695.
Jiang CF, Shi ZM, Li DM, Qian YC, Ren Y, Bai XM, et al. Estrogen-induced miR-196a elevation promotes tumor growth and metastasis via targeting SPRED1 in breast cancer. Mol Cancer 2018; 17: 83.
Belvedere R, Saggese P, Pessolano E, Memoli D, Bizzarro V, Rizzo F, et al. miR-196a is able to restore the aggressive phenotype of annexin A1 knock-out in pancreatic cancer cells by CRISPR/Cas9 genome editing. Int J Mol Sci 2018; 19: 1967.
Wentzensen N, Schiffman M, Palmer T, Arbyn M. Triage of HPV positive women in cervical cancer screening. J Clin Virol 2016; 76: 49-55.
Zheng W, Liu Z, Zhang W, Hu X. miR-31 functions as an oncogene in cervical cancer. Arch Gynecol Obstet 2015; 292: 1083-1089.
Córdova-Rivas S, Fraire-Soto I, Mercado-Casas Torres A, Servín-González LS, Granados-López AJ, López-Hernández Y, et al. 5p and 3p Strands of miR-34 Family Members Have Differential Effects in Cell Proliferation, Migration, and Invasion in Cervical Cancer Cells. Int J Mol Sci 2019; 20: 545.
Peng R, Men J, Ma R, Wang Q, Wang Y, Sun Y, et al. miR-214 down-regulates ARL2 and suppresses growth and invasion of cervical cancer cells. Biochem Biophys Res Commun 2017; 484: 623-630.
Liu P, Xin F, Ma CF. Clinical significance of serum miR-196a in cervical intraepithelial neoplasia and cervical cancer. Genet Mol Res 2015; 14: 17995-18002.
Yang L, Peng F, Qin J, Zhou H, Wang B. Downregulation of microRNA-196a inhibits human liver cancer cell proliferation and invasion by targeting FOXO1. Oncol Rep 2017; 38: 2148-2154.
Tsai MM, Wang CS, Tsai CY, Huang CG, Lee KF, Huang HW, et al. Circulating microRNA-196a/b are novel biomarkers associated with metastatic gastric cancer. Eur J Cancer 2016, 64: 137-148.
Ma Y, Wang B, Guo Y, Zhang Y, Huang S, Bao X, et al. Inhibition of miR-196a affects esophageal cancer cell growth in vitro. Biomed Pharmacother 2016, 84: 22-27.
Yu Q, Xu C, Yuan W, Wang C, Zhao P, Chen L, et al. Evaluation of plasma microRNAs as diagnostic and prognostic biomarkers in pancreatic adenocarcinoma: miR-196a and miR-210 could be negative and positive prognostic markers, respectively. Biomed Res Int 2017; 2017: 6495867.
Li JH, Luo N, Zhong MZ, Xiao ZQ, Wang JX, Yao XY, et al. Inhibition of microRNA-196a might reverse cisplatin resistance of A549/DDP non-small-cell lung cancer cell line. Tumor Biol 2016; 37: 2387-2394.

References

Cancer Genome Atlas Research Network. Integrated genomic and molecular characterization of cervical cancer. Nature 2017; 543: 378.

Ludwig N, Leidinger P, Becker K, Backes C, Fehlmann T, Pallasch C, et al. Distribution of miRNA expression across human tissues. Nucleic Acids Res 2016; 44: 3865-3877.

Reddy KB. MicroRNA (miRNA) in cancer. Cancer Cell Int 2015; 15: 38.

Pan Y, Shu X, Sun L, Yu L, Sun L, Yang Z, et al. miR"‘196a"‘5p modulates gastric cancer stem cell characteristics by targeting Smad4. Int J Oncol 2017; 50: 1965-1976.

Chen X, Du P, She J, Cao L, Li Y, Xia H. Loss of ZG16 is regulated by miR-196a and contributes to stemness and progression of colorectal cancer. Oncotarget 2016; 7: 86695.

Jiang CF, Shi ZM, Li DM, Qian YC, Ren Y, Bai XM, et al. Estrogen-induced miR-196a elevation promotes tumor growth and metastasis via targeting SPRED1 in breast cancer. Mol Cancer 2018; 17: 83.

Belvedere R, Saggese P, Pessolano E, Memoli D, Bizzarro V, Rizzo F, et al. miR-196a is able to restore the aggressive phenotype of annexin A1 knock-out in pancreatic cancer cells by CRISPR/Cas9 genome editing. Int J Mol Sci 2018; 19: 1967.

Wentzensen N, Schiffman M, Palmer T, Arbyn M. Triage of HPV positive women in cervical cancer screening. J Clin Virol 2016; 76: 49-55.

Zheng W, Liu Z, Zhang W, Hu X. miR-31 functions as an oncogene in cervical cancer. Arch Gynecol Obstet 2015; 292: 1083-1089.

Córdova-Rivas S, Fraire-Soto I, Mercado-Casas Torres A, Servín-González LS, Granados-López AJ, López-Hernández Y, et al. 5p and 3p Strands of miR-34 Family Members Have Differential Effects in Cell Proliferation, Migration, and Invasion in Cervical Cancer Cells. Int J Mol Sci 2019; 20: 545.

Peng R, Men J, Ma R, Wang Q, Wang Y, Sun Y, et al. miR-214 down-regulates ARL2 and suppresses growth and invasion of cervical cancer cells. Biochem Biophys Res Commun 2017; 484: 623-630.

Liu P, Xin F, Ma CF. Clinical significance of serum miR-196a in cervical intraepithelial neoplasia and cervical cancer. Genet Mol Res 2015; 14: 17995-18002.

Yang L, Peng F, Qin J, Zhou H, Wang B. Downregulation of microRNA-196a inhibits human liver cancer cell proliferation and invasion by targeting FOXO1. Oncol Rep 2017; 38: 2148-2154.

Tsai MM, Wang CS, Tsai CY, Huang CG, Lee KF, Huang HW, et al. Circulating microRNA-196a/b are novel biomarkers associated with metastatic gastric cancer. Eur J Cancer 2016, 64: 137-148.

Ma Y, Wang B, Guo Y, Zhang Y, Huang S, Bao X, et al. Inhibition of miR-196a affects esophageal cancer cell growth in vitro. Biomed Pharmacother 2016, 84: 22-27.

Yu Q, Xu C, Yuan W, Wang C, Zhao P, Chen L, et al. Evaluation of plasma microRNAs as diagnostic and prognostic biomarkers in pancreatic adenocarcinoma: miR-196a and miR-210 could be negative and positive prognostic markers, respectively. Biomed Res Int 2017; 2017: 6495867.

Li JH, Luo N, Zhong MZ, Xiao ZQ, Wang JX, Yao XY, et al. Inhibition of microRNA-196a might reverse cisplatin resistance of A549/DDP non-small-cell lung cancer cell line. Tumor Biol 2016; 37: 2387-2394.

Author biographies is not available.