Down-regulated HSA_circ_0003528 inhibits hepatocellular carcinoma aggressiveness via the miR-212-3p/XIAP axis

Abstract

Hepatocellular carcinoma (HCC) is characterized by a high mortality rate. Dysregulated circular RNAs (circRNAs) play a vital role in HCC. We aimed to study the role of circ_0003528 in HCC and its fundamental molecular mechanisms. HSA_circ_0003528 was identified through bioinformatics dataset analysis. The binding sites between mRNA and miRNA were predicted using online bioinformatics tools. The interaction between miR-212-3p and X-linked inhibitor of apoptosis protein ( XIAP ) or circ_0003528 was confirmed through the luciferase reporter assay. RT-qPCR and western blot assays were used to analyze the expression of all miRNAs/mRNAs and proteins. Cellular functions were evaluated using the MTT and TUNEL assays. A xenograft model was established to evaluate the function of circ_0003528 in vivo . Circ_0003528 was dramatically overexpressed in HepG2 and HUH7 cells. However, knockdown of circ_0003528 suppressed the aggressiveness of HCC cells and tumor growth both in vitro and in vivo . Furthermore, binding of miR-212-3p to circ_0003528 and XIAP was verified. Downregulation of miR-212-3p abrogated the effects of si-circ_0003528 on cell viability and apoptosis, and upregulation of XIAP antagonized the functions of the miR-212-3p mimic in HCC cells. circ_0003528 contributes to the development of HCC in vitro and in vivo via the miR-212-3p/ XIAP axis. Hence, circ_0003528 knockdown may be a potential therapeutic strategy for HCC treatment.

Knowledge mapping of MIRNA in hepatocellular carcinoma from 2012-2022:a bibliometric analysis

“…However, Sorafenib has also been associated with widespread resistance and side effects in clinical practice [35][36] . Available evidence suggests that miRNAs are involved in multiple aspects of tumor cell differentiation, proliferation, regulation, invasion, metastasis, autophagy, and tumor microenvironment [37][38][39] , and can reverse Sorafenib resistance in HCC treatment [40][41][42] and enhance the clinical e cacy of Sorafenib. Although hepatocellular carcinoma treatment has come to the era of immunotherapy in recent years, especially since the FDA has approved the combination of atelelizumab and bevacizumab for improving overall survival in patients with advanced HCC [43][44] , Sorafenib is still considered as the rst-line agent for systemic treatment of HCC.…”

Interactome of PTH-Regulated miRNAs and Their Predicted Target Genes for Investigating the Epigenetic Effects of PTH (1–34) in Bone Metabolism

“…These two miRNAs also target other pathways; of these, the Hippo signaling pathway and signaling pathways regulating the pluripotency of stem cells are most similar to the TGF-beta signaling pathway. Other pathways are not bone-related, and both miRNAs have been shown to play a role in cancer—miR-132-3p is associated with colorectal cancer [ 54 ], and miR-212-3p is associated with hepatocellular carcinoma [ 55 ]. miR-410-3p stands out in the heatmap analysis as the one that most significantly targets bone-related pathways.…”