MiR-410 affects the proliferation and apoptosis of lung cancer A549 cells through regulation of SOCS3/JAK-STAT signaling pathway

M. Li, R. Zheng, F.-L. Yuan

Department of Respiration, Yantai Yeda Hospital, Yantai, Shandong, China. h4693103829@sina.com

---

• Oncology

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.

This article has been withdrawn. The Publisher apologizes for any inconvenience this may cause.

Free PDF Download