OBJECTIVE: Janus kinase (JAK) – signal transducer and activator of transcription (STAT) signal pathway participates in regulating cell proliferation, differentiation, and apoptosis, and is correlated with non-small cell lung cancer (NSCLC) onset. Suppressors of cytokine signaling 3 (SOCS3) negatively regulates JAK-STAT pathway. SOCS3 is down-regulated in NSCLC tissues, with an elevation of miR-410 expression. This study thus intends to investigate if miR-410 plays a role in mediating NSCLC onset and underlying mechanism in this regulatory process.
PATIENTS AND METHODS: NSCLC patients were collected for tumor and adjacent tissues, among which, miR-410 and SOCS3 expression were measured. Dual luciferase reporter gene assay was employed to confirm the targeting relationship between miR-410 and SOCS3. Their expression levels were compared between A549 and BEAS-2B cells. Cultured A549 cells were treated with anti-miR-410 and/or SOCS3. Expression levels of SOCS3, p-JAK1/2, p-STAT3, and Bcl-2 were compared along with the apoptotic rate of cells.
RESULTS: Bioinformatics analysis revealed targeted binding site between miR-410 and 3’-UTR of SOCS3 mRNA. Compared to those in tumor tissues, a significant increase of miR-410 and reduction of SOCS3 were found in NSCLC tissue (p < 0.05). Dual luciferase reporter gene assay indicated that SOCS3 was targeted regulated by miR-410. Significantly higher miR-410 and lower SOCS3 levels were shown in A549 cells, compared to those in BEAS-2B cells. Transfection of anti-miR-410 and/or SOCS3 in A549 cells, SOCS3 expression and apoptosis were significantly induced, while JAK1, JAK2, and STAT3 phosphorylation were statistically decreased with the reduction of the Bcl-2 level (p < 0.05).
CONCLUSIONS: miR-410 level was increased while SOCS3 expression was declined in NSCLS tissues. MiR-410 induces the apoptosis of A549 cells through downregulating JAK/STAT3/SOCS3 signaling pathway, which provides new insights for the therapy of pulmonary carcinoma in clinic.Free PDF Download
To cite this article
M. Li, R. Zheng, F.-L. Yuan
MiR-410 affects the proliferation and apoptosis of lung cancer A549 cells through regulation of SOCS3/JAK-STAT signaling pathway
Eur Rev Med Pharmacol Sci
Vol. 22 - N. 18