Upregulation of MiR-129-5p Increases the Sensitivity to Taxol Through Inhibiting HMGB1-mediated Cell Autophagy in Breast Cancer MCF-7 Cells

Overview

Journal Braz J Med Biol Res

Specialties Biology
General Medicine

Date 2019 Oct 31

PMID 31664305

Citations 20

Authors

Ying Shi

Weihua Gong

Lu Lu

Yunfeng Wang

Jingjing Ren

Affiliations

Soon will be listed here.

Abstract

Although Taxol has improved the survival of cancer patients as a first-line chemotherapeutic agent, an increasing number of patients develop resistance to Taxol after prolonged treatment. The potential mechanisms of cancer cell resistance to Taxol are not completely clear. It has been reported that microRNAs (miRNAs) are involved in regulating the sensitivity of cancer cells to various chemotherapeutic agents. In this study, we aimed to explore the role of miR-129-5p in regulating the sensitivity of breast cancer cells to Taxol. Cell apoptosis and autophagy, and the sensitivity of MCF-7 cells to Taxol were assessed with a series of in vitro assays. Our results showed that the inhibition of autophagy increased the Taxol-induced apoptosis and the sensitivity of MCF-7 cells to Taxol. Up-regulation of miR-129-5p also inhibited autophagy and induced apoptosis. Furthermore, miR-129-5p overexpression increased the sensitivity of MCF-7 cells to Taxol. High mobility group box 1 (HMGB1), a target gene of miR-129-5p and a regulator of autophagy, was negatively regulated by miR-129-5p. We found that interference of HMGB1 enhanced the chemosensitivity of Taxol by inhibiting autophagy and inducing apoptosis in MCF-7 cells. Taken together, our findings suggested that miR-129-5p increased the chemosensitivity of MCF-7 cells to Taxol through suppressing autophagy and enhancing apoptosis by inhibiting HMGB1. Using miR-129-5p/HMGB1/autophagy-based therapeutic strategies may be a potential treatment for overcoming Taxol resistance in breast cancer.

Citing Articles

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Shao L, Zhu L, Wang M, Ning Y, Chen F, Gao X Int J Mol Med. 2023; 52(2).

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References

Schmeisser H, Bekisz J, Zoon K . New function of type I IFN: induction of autophagy. J Interferon Cytokine Res. 2014; 34(2):71-8. PMC: 3924851. DOI: 10.1089/jir.2013.0128. View

Friedman R, Farh K, Burge C, Bartel D . Most mammalian mRNAs are conserved targets of microRNAs. Genome Res. 2008; 19(1):92-105. PMC: 2612969. DOI: 10.1101/gr.082701.108. View

Shioi Y, Kashiwaba M, Inaba T, Komatsu H, Sugai T, Wakabayashi G . Long-term complete remission of metastatic breast cancer, induced by a steroidal aromatase inhibitor after failure of a non-steroidal aromatase inhibitor. Am J Case Rep. 2014; 15:85-9. PMC: 3936946. DOI: 10.12659/AJCR.890023. View

Circu M, Cardelli J, Barr M, OByrne K, Mills G, El-Osta H . Modulating lysosomal function through lysosome membrane permeabilization or autophagy suppression restores sensitivity to cisplatin in refractory non-small-cell lung cancer cells. PLoS One. 2017; 12(9):e0184922. PMC: 5612465. DOI: 10.1371/journal.pone.0184922. View

Luo J, Chen J, He L . mir-129-5p Attenuates Irradiation-Induced Autophagy and Decreases Radioresistance of Breast Cancer Cells by Targeting HMGB1. Med Sci Monit. 2016; 21:4122-9. PMC: 4700864. DOI: 10.12659/msm.896661. View

Liu Z, He K, Ma Q, Yu Q, Liu C, Ndege I . Autophagy inhibitor facilitates gefitinib sensitivity in vitro and in vivo by activating mitochondrial apoptosis in triple negative breast cancer. PLoS One. 2017; 12(5):e0177694. PMC: 5439698. DOI: 10.1371/journal.pone.0177694. View

Rowinsky E . The development and clinical utility of the taxane class of antimicrotubule chemotherapy agents. Annu Rev Med. 1997; 48:353-74. DOI: 10.1146/annurev.med.48.1.353. View

Yu Y, Zhao Y, Sun X, Ge J, Zhang B, Wang X . Down-regulation of miR-129-5p via the Twist1-Snail feedback loop stimulates the epithelial-mesenchymal transition and is associated with poor prognosis in breast cancer. Oncotarget. 2015; 6(33):34423-36. PMC: 4741463. DOI: 10.18632/oncotarget.5406. View

Liu K, Huang J, Ni J, Song D, Ding M, Wang J . MALAT1 promotes osteosarcoma development by regulation of HMGB1 via miR-142-3p and miR-129-5p. Cell Cycle. 2017; 16(6):578-587. PMC: 5384591. DOI: 10.1080/15384101.2017.1288324. View

10.

Schiff P, Horwitz S . Taxol stabilizes microtubules in mouse fibroblast cells. Proc Natl Acad Sci U S A. 1980; 77(3):1561-5. PMC: 348536. DOI: 10.1073/pnas.77.3.1561. View

11.

Liu W, Zhang Z, Zhang Y, Chen X, Guo S, Lei Y . HMGB1-mediated autophagy modulates sensitivity of colorectal cancer cells to oxaliplatin via MEK/ERK signaling pathway. Cancer Biol Ther. 2015; 16(4):511-7. PMC: 4622507. DOI: 10.1080/15384047.2015.1017691. View

12.

Chen G, Zhou N, Li J, Li T, Zhang Z, Si Z . Restoration of miR-20a expression suppresses cell proliferation, migration, and invasion in HepG2 cells. Onco Targets Ther. 2016; 9:3067-76. PMC: 4892835. DOI: 10.2147/OTT.S96861. View

13.

Chatterjee A, Chattopadhyay D, Chakrabarti G . MiR-16 targets Bcl-2 in paclitaxel-resistant lung cancer cells and overexpression of miR-16 along with miR-17 causes unprecedented sensitivity by simultaneously modulating autophagy and apoptosis. Cell Signal. 2014; 27(2):189-203. DOI: 10.1016/j.cellsig.2014.11.023. View

14.

Melvin V, Harrell C, Adelman J, Kraus W, Churchill M, Edwards D . The role of the C-terminal extension (CTE) of the estrogen receptor alpha and beta DNA binding domain in DNA binding and interaction with HMGB. J Biol Chem. 2004; 279(15):14763-71. DOI: 10.1074/jbc.M313335200. View

15.

Wang Q, Yu J . MiR-129-5p suppresses gastric cancer cell invasion and proliferation by inhibiting COL1A1. Biochem Cell Biol. 2017; 96(1):19-25. DOI: 10.1139/bcb-2016-0254. View

16.

Kubisch J, Turei D, Foldvari-Nagy L, Dunai Z, Zsakai L, Varga M . Complex regulation of autophagy in cancer - integrated approaches to discover the networks that hold a double-edged sword. Semin Cancer Biol. 2013; 23(4):252-61. DOI: 10.1016/j.semcancer.2013.06.009. View

17.

Bhattacharya A, Schmitz U, Raatz Y, Schonherr M, Kottek T, Schauer M . miR-638 promotes melanoma metastasis and protects melanoma cells from apoptosis and autophagy. Oncotarget. 2015; 6(5):2966-80. PMC: 4413631. DOI: 10.18632/oncotarget.3070. View

18.

Erol K, Baltali E, Altundag K, Guler N, Ozisik Y, Onat D . Neoadjuvant chemotherapy with cyclophosphamide, mitoxantrone, and 5-fluorouracil in locally advanced breast cancer. Onkologie. 2005; 28(2):81-5. DOI: 10.1159/000082951. View

19.

Korkmaz G, le Sage C, Tekirdag K, Agami R, Gozuacik D . miR-376b controls starvation and mTOR inhibition-related autophagy by targeting ATG4C and BECN1. Autophagy. 2012; 8(2):165-76. DOI: 10.4161/auto.8.2.18351. View

20.

Li S, Qiang Q, Shan H, Shi M, Gan G, Ma F . MiR-20a and miR-20b negatively regulate autophagy by targeting RB1CC1/FIP200 in breast cancer cells. Life Sci. 2016; 147:143-52. DOI: 10.1016/j.lfs.2016.01.044. View