miR-96-5p regulates autophagy through targeting ATG9A in lung cancer


Abstract views: 75 / PDF downloads: 39

Authors

DOI:

https://doi.org/10.5152/eurjther.2020.19116

Keywords:

Autophagy, microRNA, miR-96-5p, lung cancer

Abstract

Objective: Lung cancer is the leading cause of cancer-related deaths among all types of cancer worldwide. Autophagy is a cellular process involving lysosomal degradation of damaged organelles and long-lived proteins. It provides nutrients and energy to cancer cells by breaking down damaged proteins and organelles and contributes to tumor-cell survival by enhancing stress tolerance and supplying nutrients to meet the metabolic demands of tumors. Therefore, the combination of cytotoxic chemotherapy and autophagy inhibition strategies has been proposed. This study aimed to investigate how miR-96-5p regulates autophagy in A549 and HTB-54 lung cancer cell lines.
Methods: MiR-96-5p expression levels in lung cancer cell lines and normal bronchial epithelium were measured by qPCR. The functional role of miR-96-5p on autophagy and its modulatory effects were investigated in vitro by overexpression studies.
Results: mirR-96-5p was found to be overexpressed in A549 and HTB-54 lung cancer cell lines compared to the normal Beas2B cell line. Overexpression of miR-96-5p resulted in the attenuation of starvation-induced autophagy. It was shown that miR-96-5p suppressed autophagy by targeting ATG9A. Both mRNA and protein cellular levels of ATG9A were decreased in cells upon miR-96- 5p overexpression.
Conclusion: This study demonstrated that miR-96-5p might be a candidate for autophagy inhibition in lung cancer. The effects of autophagy inhibition by miR-96-5p and cytotoxic chemotherapy should be further examined.

Metrics

Metrics Loading ...

References

Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018; 68: 394-424.

Lu T, Yang X, Huang Y, Zhao M, Li M, Ma K, et al. Trends in the incidence, treatment, and survival of patients with lung cancer in the last four decades. Cancer Manag Res 2019; 11: 943-53.

Xue Y, Hou S, Ji H, Han X. Evolution from genetics to phenotype: reinterpretation of NSCLC plasticity, heterogeneity, and drug resistance. Protein Cell 2017; 8: 178-90.

Ktistakis NT. In praise of M. Anselmier who first used the term “autophagie” in 1859. Autophagy 2017; 13: 2015-17.

Feng Y, He D, Yao Z, Klionsky DJ. The machinery of macroautophagy. Cell Res 2014; 24: 24-41.

Parzych KR, Klionsky DJ. An overview of autophagy: morphology, mechanism, and regulation. Antioxid Redox Signal 2014; 20: 460-73.

Dikic I, Elazar Z. Mechanism and medical implications of mammalian autophagy. Nat Rev Mol Cell Biol 2018; 19: 349.

Jiang P, Mizushima N. Autophagy and human diseases. Cell Res 2014; 24: 69-79.9. Singh SS, Vats S, Chia AY-Q, Tan TZ, Deng S, Ong MS, et al. Dual role of autophagy in hallmarks of cancer. Oncogene 2018; 37: 1142-58.

Chude CI, Amaravadi RK. Targeting autophagy in cancer: update on clinical trials and novel inhibitors. Int J Mol Sci 2017; 18: 1279.

Li Y, Kowdley KV. MicroRNAs in common human diseases. Genomics Proteomics Bioinformatics 2012; 10: 246-53.

Inamura K, Ishikawa Y. MicroRNA in lung cancer: novel biomarkers and potential tools for treatment. J Clin Med 2016; 5: 36.

Chakraborty C, Sharma AR, Sharma G, Doss CGP, Lee S-S. Therapeutic miRNA and siRNA: moving from bench to clinic as next generation medicine. Mol Ther Nucleic Acids 2017; 8: 132-43.

Jing Z, Han W, Sui X, Xie J, Pan H. Interaction of autophagy with microRNAs and their potential therapeutic implications in human cancers. Cancer Lett 2015; 356: 332-8.

Paul P, Chakraborty A, Sarkar D, Langthasa M, Rahman M, Bari M, et al. Interplay between miRNAs and human diseases. J Cell Physiol 2018; 233: 2007-18.

Guttilla IK, White BA. Coordinate regulation of FOXO1 by miR-27a, miR-96, and miR-182 in breast cancer cells. J Biol Chem 2009; 284: 23204-16.

Haflidadóttir BS, Larne O, Martin M, Persson M, Edsjö A, Bjartell A, et al. Upregulation of miR-96 enhances cellular proliferation of prostate cancer cells through FOXO1. PLoS One 2013; 8: e72400.

Wu Z, Liu K, Wang Y, Xu Z, Meng J, Gu S. Upregulation of microRNA-96 and its oncogenic functions by targeting CDKN1A in bladder cancer. Cancer Cell Int 2015; 15: 107.

Xu XM, Qian JC, Deng ZL, Cai Z, Tang T, Wang P, et al. Expression of miR-21, miR-31, miR-96 and miR-135b is correlated with the clinical parameters of colorectal cancer. Oncol Lett 2012; 4: 339-45.

Fei X, Zhang J, Zhao Y, Sun M, Zhao H, Li S. miR-96 promotes invasion and metastasis by targeting GPC3 in non small cell lung cancer cells. Oncol Lett 2018; 15: 9081-6.

Shi Y, Zhao Y, Shao N, Ye R, Lin Y, Zhang N, et al. Overexpression of microRNA-96-5p inhibits autophagy and apoptosis and enhances the proliferation, migration and invasiveness of human breast cancer cells. Oncol Lett 2017; 13: 4402-12.

Yao Q, Pei Y, Zhang X, Xie B. microRNA-96 acts as a tumor suppressor gene in human osteosarcoma via target regulation of EZRIN. Life Sci 2018; 203: 1-11.

Yu N, Fu S, Liu Y, Xu Z, Liu Y, Hao J, et al. miR-96 suppresses renal cell carcinoma invasion via downregulation of Ezrin expression. J Exp Clin Cancer Res 2015; 34: 107.

Yamada T, Carson AR, Caniggia I, Umebayashi K, Yoshimori T, Nakabayashi K, et al. Endothelial nitric-oxide synthase antisense (NOS3AS) gene encodes an autophagy-related protein (APG9-like2) highly expressed in trophoblast. J Biol Chem 2005; 280: 18283-90.

Feng Y, Klionsky DJ. Autophagic membrane delivery through ATG9. Cell Res 2017; 27: 161-2.

Carlsson SR, Simonsen A. Membrane dynamics in autophagosome biogenesis. J Cell Sci 2015; 128: 193-205.

Zhou C, Ma K, Gao R, Mu C, Chen L, Liu Q, et al. Regulation of mATG9 trafficking by Src-and ULK1-mediated phosphorylation in basal and starvation-induced autophagy. Cell Res 2017; 27: 184- 201.

Kim S, Ramakrishnan R, Gabrilovich D. Impact of Radiation-Induced Autophagy on the Efficacy of Combination Radiation Therapy and Immunotherapy. International Journal of Radiation Oncology Biology Physics 2013; 87: S632.

Zhao ZQ, Yu ZY, Li J, Ouyang XN. Gefitinib induces lung cancer cell autophagy and apoptosis via blockade of the PI3K/AKT/mTOR pathway. Oncol Lett 2016; 12: 63-8.

Chen K, Shi W. Autophagy regulates resistance of non-small cell lung cancer cells to paclitaxel. Tumour Biol 2016; 37: 10539-44.

Downloads

Published

2020-12-01

How to Cite

Eroğlu, S., Işık, A. F., & Oğuzkan Balcı, S. (2020). miR-96-5p regulates autophagy through targeting ATG9A in lung cancer. European Journal of Therapeutics, 26(4), 331–336. https://doi.org/10.5152/eurjther.2020.19116

Issue

Section

Original Articles