Dysregulation of miRISC Regulatory Network Promotes Hepatocellular Carcinoma by Targeting PI3K/Akt Signaling Pathway

• Published in: International journal of molecular sciences Vol. 23; no. 19; p. 11300
• Main Authors: Kannan, Maheshkumar, Jayamohan, Sridharan, Moorthy, Rajesh Kannan, Chabattula, Siva Chander, Ganeshan, Mathan, Arockiam, Antony Joseph Velanganni
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 25.09.2022; MDPI
• Subjects: 1-Phosphatidylinositol 3-kinase; AKT protein; Angiogenesis; Apoptosis; astrocyte elevated gene-1; Autophagy; Bcl-2 protein; Carcinogenesis; Carcinogens; Cell cycle; Cell growth; cell proliferation; Flow cytometry; Gelatinase B; Gene expression; Genes; HCC; Hepatitis B; Hepatitis C; Hepatocellular carcinoma; Liver cancer; Malignancy; Medical prognosis; MicroRNAs; miR-221; p53 Protein; Protein expression; Proteins; PTEN protein; regulatory genes; RNA-induced silencing complex; RNA-mediated interference; Signal transduction; siRNA; Tumor suppressor genes; Tumors
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms231911300

Hepatocellular carcinoma (HCC) remains the third leading malignancy worldwide, causing high mortality in adults and children. The neuropathology-associated gene AEG-1 functions as a scaffold protein to correctly assemble the RNA-induced silencing complex (RISC) and optimize or increase its activity. The overexpression of oncogenic miRNAs periodically degrades the target tumor suppressor genes. Oncogenic miR-221 plays a seminal role in the carcinogenesis of HCC. Hence, the exact molecular and biological functions of the oncogene clusters miR-221/AEG-1 axis have not yet been examined widely in HCC. Here, we explored the expression of both miR-221 and AEG-1 and their target/associate genes by qRT-PCR and western blot. In addition, the role of the miR-221/AEG-1 axis was studied in the HCC by flow cytometry analysis. The expression level of the AEG-1 did not change in the miR-221 mimic, and miR-221-transfected HCC cells, on the other hand, decreased the miR-221 expression in AEG-1 siRNA-transfected HCC cells. The miR-221/AEG-1 axis silencing induces apoptosis and G2/M phase arrest and inhibits cellular proliferation and angiogenesis by upregulating p57, p53, RB, and PTEN and downregulating LSF, LC3A, Bcl-2, OPN, MMP9, PI3K, and Akt in HCC cells.