Turkish Journal of Gastroenterology
Liver - Original Article

miR-224 Regulates the Aggressiveness of Hepatoma Cells Through the IL-6/STAT3/SMAD4 Pathway


Department of Gastroenterology, Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu, China


Department of Oncology, Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu, China

Turk J Gastroenterol 2021; 32: 532-542
DOI: 10.5152/tjg.2021.191056
Read: 514 Downloads: 171 Published: 01 June 2021

Background: Previous studies have shown that miR-224 regulates the progression of liver cancer. The aim of this study was to investigate the underlying mechanisms.

Methods: The miR-224, p-STAT3 and SMAD4 expression levels were checked with tissue or/and serum samples of HCC patients by qRT-PCR or IHC methods. The regulatory role of IL-6 in p-STAT3 and SMAD4 was investigated by Western-blot. The targeted gene of miR-224 was verified by both Western-blot and luciferase reporter assay. Furthermore, the carcinogenesis of miR-224 in HCC was investigated by cell experiments in vitro and mouse xenograft model and in vivo imaging in vivo.

Results: It was found miR-224 was elevated in both tissue and serum of HCC patients. The p-STAT3 expression was higher but the SMAD4 was lower in the HCC tumor tissues. Moreover, IL-6 can induce the p-STAT3/STAT3 and miR-224 expression in HCC cells and STAT3 played the bridge role between IL-6 and miR-224. Target gene studies found miR-224 targeted the 3ʹUTR of SMAD4. Finally, the promoting roles of miR-224in the growth, proliferation, invasion and migration of HCC were discovered by in vitro and in vivo studies.

Conclusion: It implies that miR-224 may potentially represent a new target for developing novel anti-HCC therapeutics.

Cite this article as: An F, Wu X, Zhang Y, et al. miR-224 regulates the aggressiveness of hepatoma cells through the IL-6/STAT3/ SMAD4 pathway. Turk J Gastroenterol. 2021; 32(6): 532-542.

EISSN 2148-5607