| Lung cancer is one of the most deadly of all cancers.Its mortality and morbidity are among the highest among men and women.Lung cancer is divided into small cell lung cancer(SCLC)accounting for 15% and non-small cell lung cancer(NSCLC)accounting for 85%.It has the characteristics of high recurrence rate and high metastasis rate.micro RNA(miRNA)is a type of single-stranded non-coding RNA molecule,about 18 ～ 24 nucleotides(nt),which can participate in the regulation of tumors and many major diseases.Studies have shown that two mature bodies of pre-miR-199a(miR-199a-3p and miR-199a-5p)play a role in suppressing cancer in many tumors,but the mechanism in lung cancer is not yet fully understood.In this study,we found that miR-199a-3p and miR-199a-5p were down-expressed in NSCLC tissue samples,cell lines and the patient sample database.When miR-199a-3p and miR-199a-5p are over-expressed in NSCLC cell lines,apoptosis was significantly increased,cell proliferation and migration ability were suppressed,and increased the autophagy level.Through software prediction,double luciferase reporter gene and Western Blot experiments,we found that miR-199a-3p / 5p can directly target Rheb and regulate the m TOR signaling pathway.The same effect of inhibiting NSCLC appeared after down-regulating the expression of Rheb.In vivo experiments show that miR-199 a can significantly inhibit tumor growth and metastasis,which fully demonstrates that miR-199 a plays a tumor suppressive role in NSCLC.In addition,miR-199a-3p/5p has been shown to enhance the sensitivity of gefitinib to EGFR-T790 M in NSCLC-resistant cell lines(PC-9GR).In summary,this study proves that miR-199a-3p / 5p can suppress the m TOR signaling pathway by targeting Rheb,thereby inhibiting the regulatory process of NSCLC.To investigate the anti-cancer effect of pre-miR-199a/ Rheb/m TOR axis in NSCLC,that miR-199a-3p and miR-199a-3p have the potential to become an early diagnostic marker or therapeutic target for NSCLC. |
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