Inhibition of miR-221 influences bladder cancer cell proliferation and apoptosis.

OBJECTIVE: Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway participate in cell proliferation and apoptosis. Suppressors of cytokine signaling 3 (SOCS3) are negative regulators of JAK-STAT3. SOCS3 was found significantly declined, while microRNA-221 (miR-221) obviously up-regulated in bladder cancer tissue. Bioinformatics analysis revealed the complementary binding site between miR-221 and 3'- UTR of SOCS3. This study investigated the role of miR-221 in regulating SOCS3/JAK-STAT3 signaling pathway and bladder cancer cell proliferation and apoptosis. PATIENTS AND METHODS: Bladder cancer tumor tissue and para-carcinoma tissue were collected from patients to test miR-221 and SOCS3 expressions. Dual luciferase assay was used to test the targeting regulatory effect of miR-221 on SOCS3. MiR-221, SOCS3, p-JAK1, p-JAK2, and survivin expressions were compared in T24 and HBEC cells. T24 cells were divided into miR-NC, miR-221 inhibitor, pSicoR-blank, pSicoR-SOCS3, and miR-221 inhibitor + pSicoR-SOCS3 groups. Flow cytometry was applied to detect cell apoptosis. EdU staining was adopted to evaluate cell proliferation. RESULTS: MiR-221 significantly increased, while SOCS3 obviously reduced in bladder cancer tissue compared with para-carcinoma tissue. MiR-221 targeted inhibited SOCS3 expression. MiR-221, phosphorylated JAK1 (p-JAK1), phosphorylated JAK2 (p-JAK2), phosphorylated STAT3 (p-STAT3) and survivin levels markedly up-regulated, whereas SOCS3 expression apparently declined in T24 cells compared with that in HBEC cells. MiR-221 inhibitor and/or pSicoR- SOCS3 elevated SOCS3 expression, decreased p-JAK1, p-JAK2, p-STAT3 and survivin levels, enhanced cell apoptosis and attenuated cell proliferation. CONCLUSIONS: MiR-221 elevated, while SOCS3 reduced in bladder cancer tissue. Inhibition of miR-221 suppressed T24 cell proliferation and induced apoptosis by up-regulatingSOCS3 expression, lowering JAK-STAT3 signaling pathway activity and attenuating survivin expression. [ABSTRACT FROM AUTHOR]