Solamargine Induces Hepatocellular Carcinoma Cell Apoptosis and Ferroptosis via Regulating STAT1/MTCH1 Axis.

BACKGROUND: Solamargine (SM) has been shown to play anti-tumor role in hepatocellular carcinoma (HCC). However, the underlying molecular mechanisms of SM in HCC progression deserve further exploration. METHODS: HCC cell proliferation and apoptosis were assessed by cell counting kit 8 assay, colony formation assay and flow cytometry. Ferroptosis was evaluated by detecting the levels of Fe2+, iron, MDA, ROS and GSH in HCC cells. In addition, mitochondrial carrier 1 (MTCH1) mRNA level was detected by quantitative real-time PCR. Western blot was used to test MTCH1 and signal transduction and activation of transcription 1 (STAT1) protein levels. Dual-luciferase reporter assay was employed to analyze the interaction between STAT1 and MTCH1. A mouse xenograft model was also constructed to explore the role of SM in vivo. RESULTS: SM could potentially suppress HCC cell growth by inducing ferroptosis. MTCH1 was highly expressed in HCC tissues and cells, and its silencing inhibited HCC cell proliferation, promoted apoptosis and ferroptosis. MTCH1 expression was reduced by SM, and its overexpression reversed SM-induced HCC cell apoptosis and ferroptosis. Furthermore, STAT1 facilitated MTCH1 transcription and promoted its expression. Besides, STAT1 expression could be reduced by SM, and its overexpression abolished the decreasing effect of SM on MTCH1 expression. In vivo, SM suppressed HCC tumor growth by reducing MTCH1 expression. CONCLUSION: SM promoted HCC cell apoptosis and ferroptosis via the STAT1/MTCH1 axis.

LncRNA FABP5P3/miR-589-5p/ZMYND19 axis contributes to hepatocellular carcinoma cell proliferation, migration and invasion.

Hepatocellular carcinoma (HCC) contributes to cancer-related deaths greatly every year in the world. However, there is still no radical method for HCC treatment. Here we screened out a lncRNA FABP5P3 that was up-regulated in HCC tissues. Patients with higher FABP5P3 expression displayed poorer survival rate. FABP5P3 depletion in HCC cell lines and sample cells remarkably inhibited the abilities of proliferation, migration and invasion. In mechanism, we showed that FABP5P3 bond to miR-589-5p which served as a tumor suppressor. MiR-589-5p targeted directly the mRNA of ZMYND19 whose function has not been defined in HCC. FABP5P3 promoted HCC development and progression by sponging miR-589-5p and up-regulating ZMYND19 expression. In sum, we showed that FABP5P3/miR-589-5p/ZMYND19 axis regulates cell proliferation and migration in HCC, which may serve as a new target for HCC treatment.

CircRNA circ_0067934 promotes tumor growth and metastasis in hepatocellular carcinoma through regulation of miR-1324/FZD5/Wnt/ß-catenin axis.

Recently, increasing evidences demonstrate that circular RNAs (circRNAs) exert very important functions in the progression of human cancers. However, the functions and molecular mechanism of circ_0067934 in hepatocellular carcinoma (HCC) are largely unknown. In the present study, we found that the expression of circ_0067934 was significantly upregulated in HCC tissues and cell lines compared to adjacent normal tissues. Furthermore, we showed that circ_0067934 knockdown remarkably suppressed the proliferation, migration and invasion of Hep3B and HuH7 cells while inducing their apoptosis. In terms of mechanism, we found that circ_0067934 directly suppressed miR-1324, which targeted the 3'-UTR of FZD5 mRNA and subsequently downregulated the Wnt/ß-catenin signaling pathway in HCC. Through rescue experiments, we demonstrated that circ_0067934 enhanced the proliferation, migration and invasion of HCC cells by the inhibition of miR-1324 and concomitant activation of FZD5/Wnt/ß-catenin signaling pathway. In summary, the circ_0067934/miR-1324/FZD5/ß-catenin signaling axis might serve as a promising therapeutic target for HCC intervention.