Int J Biol Sci 2022; 18(10):4187-4202. doi:10.7150/ijbs.70312 This issue Cite

Research Paper

miR-199a-3p/5p regulate tumorgenesis via targeting Rheb in non-small cell lung cancer

Xiaomin Liu1#, Xianyi Wang1#, Binshu Chai1, Zong Wu1, Zhitao Gu2, Heng Zou1, Hui Zhang1, Yanli Li1, Qiangling Sun2, Wentao Fang2✉, Zhongliang Ma1✉

1. Lab for Noncoding RNA & Cancer, School of Life Sciences, Shanghai University, Shanghai 200444, China.
2. Department of Thoracic Surgery, Thoracic Cancer Institute, Shanghai Chest Hospital, Jiaotong University Medical School,Shanghai 200030, China.
# Equal contribution

Citation:
Liu X, Wang X, Chai B, Wu Z, Gu Z, Zou H, Zhang H, Li Y, Sun Q, Fang W, Ma Z. miR-199a-3p/5p regulate tumorgenesis via targeting Rheb in non-small cell lung cancer. Int J Biol Sci 2022; 18(10):4187-4202. doi:10.7150/ijbs.70312. https://www.ijbs.com/v18p4187.htm
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Abstract

Graphic abstract

Lung cancer is one of the deadliest cancers, in which non-small cell lung cancer (NSCLC) accounting for 85% and has a low survival rate of 5 years. Dysregulation of microRNAs (miRNAs) can participate in tumor regulation and many major diseases. In this study, we found that miR-199a-3p/5p were down-expressed in NSCLC tissue samples, cell lines, and the patient sample database. MiR-199a-3p/5p overexpression could significantly suppress cell proliferation, migration ability and promote apoptosis. Through software prediction, ras homolog enriched in brain (Rheb) was identified as a common target of miR-199a-3p and miR-199a-5p, which participated in regulating mTOR signaling pathway. The same effect of inhibiting NSCLC appeared after down-regulating the expression of Rheb. Furthermore, our findings revealed that miR-199a can significantly inhibit tumor growth and metastasis in vivo, which fully demonstrates that miR-199a plays a tumor suppressive role in NSCLC. In addition, miR-199a-3p/5p has been shown to enhance the sensitivity of gefitinib to EGFR-T790M in NSCLC. Collectively, these results prove that miR-199a-3p/5p can act as cancer suppressor genes to inhibit the mTOR signaling pathway by targeting Rheb, which in turn inhibits the regulatory process of NSCLC. Thus, to investigate the anti-cancer effect of pre-miR-199a/Rheb/mTOR axis in NSCLC, miR-199a-3p and miR-199a-5p have the potential to become an early diagnostic marker or therapeutic target for NSCLC.

Keywords: NSCLC, miR-199a-3p/5p, Rheb, tumor suppressor, tumor resistance


Citation styles

APA
Liu, X., Wang, X., Chai, B., Wu, Z., Gu, Z., Zou, H., Zhang, H., Li, Y., Sun, Q., Fang, W., Ma, Z. (2022). miR-199a-3p/5p regulate tumorgenesis via targeting Rheb in non-small cell lung cancer. International Journal of Biological Sciences, 18(10), 4187-4202. https://doi.org/10.7150/ijbs.70312.

ACS
Liu, X.; Wang, X.; Chai, B.; Wu, Z.; Gu, Z.; Zou, H.; Zhang, H.; Li, Y.; Sun, Q.; Fang, W.; Ma, Z. miR-199a-3p/5p regulate tumorgenesis via targeting Rheb in non-small cell lung cancer. Int. J. Biol. Sci. 2022, 18 (10), 4187-4202. DOI: 10.7150/ijbs.70312.

NLM
Liu X, Wang X, Chai B, Wu Z, Gu Z, Zou H, Zhang H, Li Y, Sun Q, Fang W, Ma Z. miR-199a-3p/5p regulate tumorgenesis via targeting Rheb in non-small cell lung cancer. Int J Biol Sci 2022; 18(10):4187-4202. doi:10.7150/ijbs.70312. https://www.ijbs.com/v18p4187.htm

CSE
Liu X, Wang X, Chai B, Wu Z, Gu Z, Zou H, Zhang H, Li Y, Sun Q, Fang W, Ma Z. 2022. miR-199a-3p/5p regulate tumorgenesis via targeting Rheb in non-small cell lung cancer. Int J Biol Sci. 18(10):4187-4202.

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