miR-140-3p enhances the sensitivity of LUAD cells to antitumor agents by targeting the ADAM10/Notch pathway

Meng, Hao; Li, Bo; Xu, Wei; Ding, Renquan; Xu, Shiguang; Wu, Qiong; Zhang, Yingshi

doi:10.7150/jca.78835



International Journal of Biological Sciences

International Journal of Medical Sciences

Theranostics

Journal of Genomics

Nanotheranostics

Global reach, higher impact

Full Text | PDF

J Cancer 2022; 13(15):3660-3673. doi:10.7150/jca.78835 This issue Cite

Research Paper

miR-140-3p enhances the sensitivity of LUAD cells to antitumor agents by targeting the ADAM10/Notch pathway

Hao Meng^1*, Bo Li^1*, Wei Xu^1*, Renquan Ding¹, Shiguang Xu^1✉, Qiong Wu^1✉, Yingshi Zhang^2✉

1. Department of Thoracic Surgery, General Hospital of Northern Theater Command, Shenyang City 110011, Liaoning Province, China.
2. Department of Clinical Pharmacy, Shenyang Pharmaceutical University, Shenyang City 110011, Liaoning Province, China.
*These authors equally contributed to this work.

✉ Corresponding authors: Dr. and prof. Shiguang Xu (E-mail: xsg13309884079com); Department of Thoracic Surgery, General Hospital of Northern Theater Command, No.83, Wenhua Road, Shenhe District, Shenyang City 110016, Liaoning Province, China. Qio More

Citation:

Meng H, Li B, Xu W, Ding R, Xu S, Wu Q, Zhang Y. miR-140-3p enhances the sensitivity of LUAD cells to antitumor agents by targeting the ADAM10/Notch pathway. J Cancer 2022; 13(15):3660-3673. doi:10.7150/jca.78835. https://www.jcancer.org/v13p3660.htm

Other styles

Abstract

Background: The Notch pathway, which is related to the drug-resistance of lung adenocarcinoma (LUAD) type of non-small cell lung cancer (NSCLC) cells, is activated by cleavage of Notch proteins mediated by ADAMs, ADAM10 or ADAM17.

Methods: In the present study, our results demonstrated that of these two ADAMs, the expression of ADAM10 in clinical samples of the LUAD type of NSCLC was much higher than that of ADAM17, while miR-140-3p - an miRNA that could target ADAM10 - was identified by an online tool: miRDB (miRNA database). The detail function and mechanism of miR-140-3p in regulating the sensitivity of NSCLC cells to antitumor drugs was systematically explored in vitro and in vivo.

Results: In A549, a typical NSCLC LUAD cell line, miR-140-3p decreased ADAM10 expression and repressed activation of the Notch pathway by repressing cleavage of Notch proteins. The expression of miR-140-3p was negatively related to ADAM10 in clinical specimens. Nucleocytoplasmic separation/subfraction assays showed that miR-140-3p was able to inhibit the cleavage of Notch protein, and led to the accumulation of Notch intracellular domains (NICD) in the nucleus. Overexpression of miR-140-3p enhanced the sensitivity of A549 cells to antitumor agents by targeting the 3'UTR region of ADAM10 mRNA in both cultured cells and in vivo models.

Conclusion: ADAM10 plays a major role in LUAD, and miR-140-3p acts on ADAM10 and inhibits its expression and the cleavage of Notch protein, leading to the inhibition the activity of the Notch pathway, and ultimately upregulating LUAD cell sensitivity to anti- tumor drugs.

Keywords: Notch pathway, A disintegrin and metalloproteinase domain 10, miR-140-3p, chemotherapeutic agents, molecular targeted agents

Citation styles

APA

Meng, H., Li, B., Xu, W., Ding, R., Xu, S., Wu, Q., Zhang, Y. (2022). miR-140-3p enhances the sensitivity of LUAD cells to antitumor agents by targeting the ADAM10/Notch pathway. Journal of Cancer, 13(15), 3660-3673. https://doi.org/10.7150/jca.78835.

ACS

Meng, H.; Li, B.; Xu, W.; Ding, R.; Xu, S.; Wu, Q.; Zhang, Y. miR-140-3p enhances the sensitivity of LUAD cells to antitumor agents by targeting the ADAM10/Notch pathway. J. Cancer 2022, 13 (15), 3660-3673. DOI: 10.7150/jca.78835.

NLM

CSE

Meng H, Li B, Xu W, Ding R, Xu S, Wu Q, Zhang Y. 2022. miR-140-3p enhances the sensitivity of LUAD cells to antitumor agents by targeting the ADAM10/Notch pathway. J Cancer. 13(15):3660-3673.

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.