The mechanism of mucin 1 gene by regulated janus protein tyrosine kinase/signal transducer and activators of transcription 3 signaling pathway to inhibit proliferation and promote apoptosis of thyroid cancer cells

Abstract

Objective To investigate the mechanism of membrane type mucin 1 (MUC1) gene by regulated janus protein tyrosine kinase/signal transducer and activators of transcription 3 (JAK/STAT3) signaling pathway to inhibit proliferation and promote apoptosis of thyroid cancer cells. Methods The expression of MUC1 in thyroid carcinoma and adjacent tissues was detected by Western blotting, MUC1 small interfering RNA (MUC1-siRNA) and negative control (siRNA-NC) were transfected into human thyroid cancer cells SW579, empty cells as the control group; cells were transfected for 48 h, Western blotting was used to detect transfection effect; cell proliferation was detected by cell counting kit-8 (CCK-8); cell apoptosis was detected by flow cytometry; the expression of B cell lymphoma/leukemia-2 associated X protein (bax), B cell lymphoma/leukemia-2 (bcl-2), STAT3, phosphorylated STAT3 (p-STAT3) protein was detected by Western blotting; 15 μmol/L AG490 specific inhibitor of JAK/STAT3 signaling pathway to join cells as the inhibitor group, without inhibitors for the untreated group, cell proliferation and apoptosis in two group was detected by CCK-8 and flow cytometry separately; the expression of bax, bcl-2, STAT3, p-STAT3 protein was detected by Western blotting. Results The expression of MUC1 in thyroid carcinoma tissues (0.434±0.034)was significantly higher than that in paracancerous tissues (0.153±0.018, t=12.651, P=0.000); the cell survival rate [(55.38±7.12)%] and bcl-2 (0.237±0.031), p-STAT3 (0.045±0.013) protein expression in MUC1-siRNA group was significantly lower than the control group [(94.32±5.21)%, 0.425±0.034, 0.122±0.025], cell apoptosis rate [(16.29±1.23)%] and bax (0.248±0.026) protein expression was significantly higher than the control group [(3.06±0.78)%, 0.109±0.019; tSurvival rate=7.645, PSurvival rate=0.002; tbcl-2=7.077, Pbcl-2=0.002; tp-STAT3=4.733, Pp-STAT3=0.009; tApoptosis rate=15.733, PApoptosis rate=0.000; tbax=7.476, Pbax=0.002]. The proliferation and apoptosis of the cells after inhibitor adding were agreed with the results of MUC1-siRNA. Conclusion To silence the expression of MUC1 can significantly inhibit the proliferation of human thyroid carcinoma SW579 cells, and induce cell apoptosis by regulating the ratio of bcl-2/bax, and its mechanism was related to regulation of JAK/STAT3 signaling pathway. Key words: Mucin 1 gene; Thyroid carcinoma; Proliferation; Apoptosis