<p>microRNA-519d Induces Autophagy and Apoptosis of Human Hepatocellular Carcinoma Cells Through Activation of the AMPK Signaling Pathway via Rab10</p>

Abstract

Background and Aim: Hepatocellular carcinoma (HCC) is a type of cancer with high mortality rates. The overexpression of microRNA-519d (miR-519d) has been explored in different types of cancers, which could significantly help suppress cancer development. This study aimed to investigate the interaction of miR-519d with its target gene, Rab10, as well as its effects on cell proliferation and autophagy in HCC cells through modulation of the AMPK signaling pathway. Methods: Microarray analysis was used to analyze the differentially expressed genes in HCC, and the target genes of the screened-out miRNA were predicted and verified. The expression of miR-519d and Rab10, AMPK signaling pathway-related proteins, apoptosisand autophagy-related proteins was determined by RT-qPCR and Western blot analysis in HCC tissues and cell lines. Lastly, the effects of miR-519d and Rab10 in HCC cell proliferation, apoptosis, and mouse tumour xenograft in vivo were examined through gainand loss-of-function experiments. Results: MiR-519d was down-regulated and Rab10 was upregulated in HCC tissues and cell lines. Overexpression of miR-519d decreased the expression of Rab10, mTOR, and Bcl-2, but increased the expression of Bax, Beclin1, Atg5, and p53. Upregulated miR-519d and downregulated Rab10 expression suppressed cell proliferation and induced cell apoptosis and autophagy in HCC cells. Finally, upregulation of miR-519d inhibited tumour growth in vivo. Conclusion: The result obtained in this study indicates that up-regulation of miR-519d inhibits proliferation and promotes apoptosis and autophagy of HCC cells through activation of the AMPK signaling pathway via downregulating Rab10, which provides a potential target for the treatment of HCC.

FAM49B Promotes Breast Cancer Proliferation, Metastasis , and Chemoresistance by Stabilizing ELAVL1 Protein and Regulating Downstream Rab10/TLR4 Pathway

“…Rab10 is a protein coding gene with GTP-and GDP-binding domains and belongs to the RAS superfamily of small GTPases [33,34]. A recent study demonstrated that Rab10 was highly expressed in liver cancer tissue samples [35,36]. Furthermore, inhibition of Rab10 represses osteosarcoma cell proliferation and metastasis [37].…”

Identification of SARS-CoV-2 Proteins Binding Human mRNAs As a Novel Signature Predicting Overall Survival in Hepatocellular Carcinoma

“…RAB10, Ras-related protein Rab-10, belongs to the Rab family, and could contribute to glioma cell proliferation (Shen et al, 2020). More importantly, in HCC cells through binding to Rab10, upregulation of miR-519d suppresses cell proliferation and promotes apoptosis and autophagy through activation of the AMP-activated protein kinase (AMPK) signaling pathway (Zhang et al, 2020). STC2 was upregulated in HCC tissues and silencing of endogenous STC2 resulted in a reduced cell growth by cell cycle delay in G0/G1 phase in HCC (Wang et al, 2012).…”

<p>Hypoxia-Induced Placenta-Specific microRNA (miR-512-3p) Promotes Hepatocellular Carcinoma Progression by Targeting Large Tumor Suppressor Kinase 2</p>

“…MicroRNAs are involved in the regulation of HCC progression. 45,46 The In HCC Hippo signaling acts as a cancer suppression pathway by inhibiting tumor-related processes, including proliferation, 48 migration, 49 and invasion. 50 In the Hippo pathway LATS kinases phosphorylate YAP and cause the cytoplasmic retention and degradation of YAP.…”