AEG-1/miR-221 Axis Cooperatively Regulates the Progression of Hepatocellular Carcinoma by Targeting PTEN/PI3K/AKT Signaling Pathway

• Published in: International journal of molecular sciences Vol. 20; no. 22; p. 5526
• Main Authors: Kannan, Maheshkumar, Jayamohan, Sridharan, Moorthy, Rajesh Kannan, Chabattula, Siva Chander, Ganeshan, Mathan, Arockiam, Antony Joseph Velanganni
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.11.2019; MDPI
• Subjects: 1-Phosphatidylinositol 3-kinase; AKT protein; Analysis; Angiogenesis; Antigens; Apoptosis; Apoptosis - genetics; astrocyte elevated gene-1; Autophagy; Autophagy - genetics; Bcl-2 protein; California; Cancer therapies; Carcinogenesis; Carcinogens; Carcinoma, Hepatocellular - blood supply; Carcinoma, Hepatocellular - genetics; Carcinoma, Hepatocellular - pathology; Cell adhesion & migration; Cell cycle; Cell Cycle - genetics; Cell Cycle Checkpoints - genetics; Cell growth; Cell Line, Tumor; Cell Movement - genetics; Cell proliferation; Cell Proliferation - genetics; Chemotherapy; Developing countries; Development and progression; Disease; Disease Progression; Down-Regulation - genetics; Gelatinase B; Gene expression; Gene Expression Regulation, Neoplastic; Genes; hcc; Health aspects; Hepatitis; Hepatocellular carcinoma; Hepatoma; Humans; India; LDCs; Liver cancer; Liver Neoplasms - blood supply; Liver Neoplasms - genetics; Liver Neoplasms - pathology; Membrane Proteins - metabolism; MicroRNA; MicroRNAs; MicroRNAs - genetics; MicroRNAs - metabolism; mir-221; Mortality; Neoplasm Invasiveness; Neovascularization, Pathologic - genetics; p53 Protein; Phosphatidylinositol 3-Kinases - metabolism; Protein expression; Proteins; Proto-Oncogene Proteins c-akt - metabolism; PTEN Phosphohydrolase - metabolism; PTEN protein; regulatory proteins; Retinoblastoma protein; Risk factors; RNA, Messenger - genetics; RNA, Messenger - metabolism; RNA-Binding Proteins - metabolism; Signal Transduction; Studies; Tumor necrosis factor-TNF; Tumor proteins; Wound healing; California; India; HCC; regulatory proteins; cell proliferation; astrocyte elevated gene-1; miR-221
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms20225526

Hepatocellular carcinoma (HCC) is the third leading malignancy worldwide, causing mortality in children and adults. AEG-1 is functioned as a scaffold protein for the proper assembly of RNA-induced silencing complex (RISC) to optimize or increase its activity. The increased activity of oncogenic miRNAs leads to the degradation of target tumor suppressor genes. miR-221 is an oncogenic miRNA, that plays a seminal role in carcinogenesis regulation of HCC. However, the molecular mechanism and biological functions of the miR-221/AEG-1 axis have not been investigated extensively in HCC. Here, the expression of miR-221/AEG-1 and their target/associate genes was analyzed by qRT-PCR and Western blot. The role of the miR-221/AEG-1 axis in HCC was evaluated by proliferation assay, migration assay, invasion assay, and flow cytometry analysis. The expression level of miR-221 decreased in AEG-1 siRNA transfected HCC cells. On the other hand, there were no significant expression changes of AEG-1 in miR-221 mimic and miR-221 inhibitor transfected HCC cells and inhibition of miR-221/AEG-1 axis decreased cell proliferation, invasion, migration, and angiogenesis and induced apoptosis, cell cycle arrest by upregulating p57, p53, PTEN, and RB and downregulating LSF, MMP9, OPN, Bcl-2, PI3K, AKT, and LC3A in HCC cells. Furthermore, these findings suggest that the miR-221/AEG-1 axis plays a seminal oncogenic role by modulating PTEN/PI3K/AKT signaling pathway in HCC. In conclusion, the miR-221/AEG-1 axis may serve as a potential target for therapeutics, diagnostics, and prognostics of HCC.