MiR-153-5p Enhances the Sensitivity of Triple-Negative Breast Cancer Cells to Paclitaxel by Inducing G2M Phase Arrest

Overview

Journal Onco Targets Ther

Publisher Dove Medical Press

Specialty Oncology

Date 2020 Jun 5

PMID 32494162

Citations 5

Authors

Yang Wang

Nan Wu

Jun Zhang

Huidong Wang

Xiaojuan Men

Affiliations

Soon will be listed here.

Abstract

Background: Paclitaxel (PTX) resistance is a main obstacle for the treatment of triple-negative breast cancers (TNBC). Evidences have shown that miR-153-5p could induce the apoptosis of breast cancer cells. Thus, this study aimed to investigate the effect of miR-153-5p on PTX-resistance TNBC cells.

Methods: Cell Counting Kit-8, flow cytometry and wound healing assays were used to detect the viability, apoptosis and migration of MDA-MB-231/PTX cells, respectively. The luciferase reporter assay was used to explore the potential binding targets of miR-153-5p. The expressions of CDK1, cyclin B1 and p-Akt in MDA-MB-231/PTX cells were detected with Western blot. In vivo animal study was performed finally.

Results: In this study, the inhibitory effects of PTX on the proliferation and migration of MDA-MB-231/PTX cells were significantly enhanced following transfection with miR-153-5p. In addition, overexpression of miR-153-5p markedly enhanced the pro-apoptotic effect of PTX on MDA-MB-231/PTX cells. Luciferase reporter assay validated that cyclin-dependent kinase 1 (CDK1) was a potential binding target of miR-153-5p. Moreover, overexpression of miR-153-5p prominently increased PTX-induced cell cycle arrest at G2/M phase in MDA-MB-231/PTX cells via downregulation of CDK1, cyclin B1 and p-Akt. In vivo experiments confirmed that overexpression of miR-153-5p notably enhanced PTX sensitivity in MDA-MB-231/PTX xenograft model.

Conclusion: We found that overexpression of miR-153-5p could reverse PTX resistance in PTX-resistant TNBC cells via inducing G2/M phase arrest, indicating that miR‑153-5p may be a promising agent for patients with PTX-resistant TNBC.

Citing Articles

Long non-coding RNA MIMT1 promotes retinoblastoma proliferation via sponging miR-153-5p to upregulate FGF2.

Wang B, Cai R, Sun T, Yang Z, Zhang H Heliyon. 2024; 10(13):e34243.

PMID: 39091947 PMC: 11292528. DOI: 10.1016/j.heliyon.2024.e34243.

LINC01354 enhances the metastatic ability of gastric cancer cells by adjusting miR-153-5p/CADM2 expression.

Fang F, Gu Y, Gao J, An L, Kang J, Mu Q Am J Cancer Res. 2023; 13(6):2630-2643.

PMID: 37424819 PMC: 10326585.

Comprehensive landscape of the miRNA-regulated prognostic marker LAYN with immune infiltration and stemness in pan-cancer.

Jiawen W, Jinfu W, Jianyong L, Yaoguang Z, Jianye W J Cancer Res Clin Oncol. 2023; 149(13):10989-11011.

PMID: 37335337 DOI: 10.1007/s00432-023-04986-7.

LPCAT1 is transcriptionally regulated by FOXA1 to promote breast cancer progression and paclitaxel resistance.

Zhang H, Zheng Y Oncol Lett. 2023; 25(4):134.

PMID: 36909375 PMC: 9996177. DOI: 10.3892/ol.2023.13720.

A comprehensive review on miR-153: Mechanistic and controversial roles of miR-153 in tumorigenicity of cancer cells.

Yousefnia S Front Oncol. 2022; 12:985897.

PMID: 36158686 PMC: 9500380. DOI: 10.3389/fonc.2022.985897.

References

Dai X, Zhang S, Cheng H, Cai D, Chen X, Huang Z . FA2H Exhibits Tumor Suppressive Roles on Breast Cancers via Cancer Stemness Control. Front Oncol. 2019; 9:1089. PMC: 6821679. DOI: 10.3389/fonc.2019.01089. View

Wang Y, Sui Y, Tao Y . Gambogic acid increases the sensitivity to paclitaxel in drug‑resistant triple‑negative breast cancer via the SHH signaling pathway. Mol Med Rep. 2019; 20(5):4515-4522. PMC: 6797991. DOI: 10.3892/mmr.2019.10697. View

Wang X, Lo C, Chen L, Ngan E, Xu A, Poon R . CDK1-PDK1-PI3K/Akt signaling pathway regulates embryonic and induced pluripotency. Cell Death Differ. 2016; 24(1):38-48. PMC: 5260505. DOI: 10.1038/cdd.2016.84. View

Xu W, Li J, Tian H, Wang R, Feng Y, Tang J . MicroRNA‑186‑5p mediates osteoblastic differentiation and cell viability by targeting CXCL13 in non‑traumatic osteonecrosis. Mol Med Rep. 2019; 20(5):4594-4602. PMC: 6797973. DOI: 10.3892/mmr.2019.10710. View

Liao W, Ho Y, Lin Y, Raj E, Liu K, Chen C . Targeting EGFR of triple-negative breast cancer enhances the therapeutic efficacy of paclitaxel- and cetuximab-conjugated nanodiamond nanocomposite. Acta Biomater. 2019; 86:395-405. DOI: 10.1016/j.actbio.2019.01.025. View

Yao J, Yao X, Tian T, Fu X, Wang W, Li S . ABCB5-ZEB1 Axis Promotes Invasion and Metastasis in Breast Cancer Cells. Oncol Res. 2017; 25(3):305-316. PMC: 7841086. DOI: 10.3727/096504016X14734149559061. View

Han L, Cui D, Li B, Xu W, Lam A, Chan K . MicroRNA-338-5p reverses chemoresistance and inhibits invasion of esophageal squamous cell carcinoma cells by targeting Id-1. Cancer Sci. 2019; 110(12):3677-3688. PMC: 6890449. DOI: 10.1111/cas.14220. View

Zasadil L, Andersen K, Yeum D, Rocque G, Wilke L, Tevaarwerk A . Cytotoxicity of paclitaxel in breast cancer is due to chromosome missegregation on multipolar spindles. Sci Transl Med. 2014; 6(229):229ra43. PMC: 4176609. DOI: 10.1126/scitranslmed.3007965. View

Zuo Z, Ye F, Liu Z, Huang J, Gong Y . MicroRNA-153 inhibits cell proliferation, migration, invasion and epithelial-mesenchymal transition in breast cancer via direct targeting of RUNX2. Exp Ther Med. 2019; 17(6):4693-4702. PMC: 6488978. DOI: 10.3892/etm.2019.7470. View

10.

Wu X, Li L, Li Y, Liu Z . MiR-153 promotes breast cancer cell apoptosis by targeting HECTD3. Am J Cancer Res. 2016; 6(7):1563-71. PMC: 4969405. View

11.

Wee Z, Yatim S, Kohlbauer V, Feng M, Goh J, Bao Y . IRAK1 is a therapeutic target that drives breast cancer metastasis and resistance to paclitaxel. Nat Commun. 2015; 6:8746. PMC: 4640083. DOI: 10.1038/ncomms9746. View

12.

Pan Z, Zhang X, Yu P, Chen X, Lu P, Li M . Cinobufagin Induces Cell Cycle Arrest at the G2/M Phase and Promotes Apoptosis in Malignant Melanoma Cells. Front Oncol. 2019; 9:853. PMC: 6738445. DOI: 10.3389/fonc.2019.00853. View

13.

Wei D, Yu G, Zhao Y . MicroRNA-30a-3p inhibits the progression of lung cancer via the PI3K/AKT by targeting DNA methyltransferase 3a. Onco Targets Ther. 2019; 12:7015-7024. PMC: 6717841. DOI: 10.2147/OTT.S213583. View

14.

Dent R, Trudeau M, Pritchard K, Hanna W, Kahn H, Sawka C . Triple-negative breast cancer: clinical features and patterns of recurrence. Clin Cancer Res. 2007; 13(15 Pt 1):4429-34. DOI: 10.1158/1078-0432.CCR-06-3045. View

15.

Li Y, Quan J, Chen F, Pan X, Zhuang C, Xiong T . MiR-31-5p acts as a tumor suppressor in renal cell carcinoma by targeting cyclin-dependent kinase 1 (CDK1). Biomed Pharmacother. 2019; 111:517-526. DOI: 10.1016/j.biopha.2018.12.102. View

16.

Li Y, Liang Y, Sang Y, Song X, Zhang H, Liu Y . MiR-770 suppresses the chemo-resistance and metastasis of triple negative breast cancer via direct targeting of STMN1. Cell Death Dis. 2018; 9(1):14. PMC: 5849036. DOI: 10.1038/s41419-017-0030-7. View

17.

Krol J, Loedige I, Filipowicz W . The widespread regulation of microRNA biogenesis, function and decay. Nat Rev Genet. 2010; 11(9):597-610. DOI: 10.1038/nrg2843. View

18.

Gluz O, Liedtke C, Gottschalk N, Pusztai L, Nitz U, Harbeck N . Triple-negative breast cancer--current status and future directions. Ann Oncol. 2009; 20(12):1913-27. DOI: 10.1093/annonc/mdp492. View

19.

Jiang J, Liu Y, Zhao Y, Tian F, Wang G . miR-153-3p Suppresses Inhibitor of Growth Protein 2 Expression to Function as Tumor Suppressor in Acute Lymphoblastic Leukemia. Technol Cancer Res Treat. 2019; 18:1533033819852990. PMC: 6542125. DOI: 10.1177/1533033819852990. View

20.

Sun H, Zhou X, Bao Y, Xiong G, Cui Y, Zhou H . Involvement of miR-4262 in paclitaxel resistance through the regulation of PTEN in non-small cell lung cancer. Open Biol. 2019; 9(7):180227. PMC: 6685930. DOI: 10.1098/rsob.180227. View