Details

Autor(en) / Beteiligte

• Huang, Shan
• Zhou, Da
• Li, Yu‐Xuan
• Ming, Zhi‐Yong
• Li, Ke‐Zhi
• Wu, Guo‐Bin
• Chen, Chuang
• Zhao, Yin‐Nong

Titel

In vivo and in vitro effects of microRNA‐221 on hepatocellular carcinoma development and progression through the JAK–STAT3 signaling pathway by targeting SOCS3

Ist Teil von

• Journal of cellular physiology, 2019-04, Vol.234 (4), p.3500-3514

Ort / Verlag

United States

Erscheinungsjahr

2019

Quelle

Wiley Online Library - AutoHoldings Journals

Beschreibungen/Notizen

• Hepatocellular carcinoma (HCC), as the third leading cancer‐caused deaths, prevails with high mortality, and affects more than half a million individuals per year worldwide. A former study revealed that microRNA‐221 (miR‐221) was involved in cell proliferation of liver cancer and HCC development. The current study aims to evaluate whether miR‐221 targeting SOCS3 affects HCC through JAK–STAT3 signaling pathway. A series of miR‐221 mimic, miR‐221 inhibitor, siRNA against SOCS3, and SOCS3 plasmids were introduced to SMMC7721 cells with the highest miR‐221 expression assessed. The expression of JAK–STAT3 signaling pathway–related genes and proteins was determined by Western blot analysis. Cell apoptosis, viability, migration, and invasion were evaluated by means of flow cytometry, 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5 diphenyl tetrazolium bromide, and transwell assays, respectively. HCC xenograft in nude mice was performed to measure HCC tumor growth. miR‐221 was found to be highly expressed but SOCS3 was poorly expressed in HCC tissues. miR‐221 expression was correlated with lymph node metastasis (LNM) and tumor node metastasis (TNM) of HCC, and SOCS3 expression was correlated with LNM, differentiation and TNM of HCC. SOCS3 is a target gene of miR‐221. MiR‐221 mimic or si‐SOCS3 exposure was found to induce cell viability, migration, and invasion, and reduce apoptosis. MiR‐221 inhibitor was observed to have inhibitory effects on HCC cell proliferation, migration, and invasion. Moreover, the expression of JAK–STAT3 signaling pathway was suppressed by miR‐221 inhibitor. Downregulated miR‐221 expression could promote its target gene SOCS3 to inhibit the proliferation, invasion and migration of HCC cells by repressing JAK–STAT3 signaling pathway. Downregulated microRNA‐221 expression could promote its target gene SOCS3 to inhibit the proliferation, invasion, and migration of HCC cells by repressing JAK–STAT3 signaling pathway.