Oncotarget

Research Papers:

MiR-29b reverses oxaliplatin-resistance in colorectal cancer by targeting SIRT1

Hui Liu _ and Xin-Hua Cheng

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Oncotarget. 2018; 9:12304-12315. https://doi.org/10.18632/oncotarget.24380

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Abstract

Hui Liu1 and Xin-Hua Cheng1

1Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China

Correspondence to:

Xin-Hua Cheng, email: xinhua_2015@163.com

Keywords: colorectal cancer, acquired drug resistance, oxaliplatin, miR-29b, SIRT1

Received: June 29, 2017     Accepted: September 23, 2017     Published: February 01, 2018

ABSTRACT

Oxaliplatin is a commonly used chemotherapeutic drug for the treatment of advanced colorectal cancer. However, acquired drug resistance against oxaliplatin remains a major obstacle for efficient use of it, and mechanisms underlying oxaliplatin resistance are still required to be explored. In the present study, we exposed colorectal cancer cell line SW480 to oxaliplatin for a long time to obtain oxaliplatin-resistant colorectal cancer cell model (OR-SW480). We found that intracellular expression of miR-29b was decreased when the SW480 cells became oxaliplatin-resistant. More importantly, overexpression of miR-29b resensitized OR-SW480 cells to oxaliplatin treatment. Mechanically, gene of SIRT1 was identified to be the target of miR-29b. Overexpression of miR-29b in oxaliplatin-treated OR-SW480 decreased the expression of SIRT1 to enhance the ROS production and JNK phosphorylation, and thus promoting apoptosis via activation of caspase 9, 7 and 3. On the other hand, expression plasmid of SIRT1, N-acetyl cysteine or SP600125 (JNK specific inhibitor) abolished the effect of miR-29b on oxaliplatin-treated OR-SW480. We therefore demonstrated that miR-29b reverses oxaliplatin-resistance in colorectal cancer by targeting SIRT1/ROS/JNK pathway.


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