AEG-1/miR-221 Axis Cooperatively Regulates the Progression of Hepatocellular Carcinoma by Targeting PTEN/PI3K/AKT Signaling Pathway
Authors: Maheshkumar Kannan
Sridharan Jayamohan
Rajesh Kannan Moorthy
Siva Chander Chabattula
Mathan Ganeshan
Antony Joseph Velanganni Arockiam
Journal: International Journal of Molecular Sciences (2019)
Discipline: CHEMISTRY
Keywords: HCC; astrocyte elevated gene-1; cell proliferation; miR-221; regulatory proteins.
Affiliations: Molecular Oncology Laboratory, Department of Biochemistry, School of Life Sciences, Bharathidasan University, Tiruchirappalli 620024, India., Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras, Chennai 600036, India., Cancer Biology Laboratory, Department of Biomedical Science, School of Life Sciences, Bharathidasan University, Tiruchirappalli 620024, India.

Abstract:  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. 

Retracted: Yes

PubPeer comments:
 Several images from figures 4 and 5 are unexpectedly similar     Figure 5 description:  The transwell invasion assay with Matrigel (A) and migration assay without Matrigel (B) were performed in miR-221 mimic, miR-221 inhibitor, AEG-1 siRNA and their controls transfected HCC cells. , 
 Retracted [14 June 2022] . ------------------------- The journal retracts the article, u201cAEG-1 miR-221 Axis Cooperatively Regulates the Progression of Hepatocellular Carcinoma by Targeting PTEN PI3K AKT Signaling Pathwayu201d [1], cited above. We have been made aware that a number of figures in the paper cited above [1] contain manipulation. Several images from Figures 4 and 5 are unexpectedly similar. In accordance with our ethics procedures, an investigation was conducted. The authors have not been able to provide a satisfactory explanation for these irregularities, which brings uncertainty regarding the scientific conclusions. Therefore, to ensure the addition of only high-quality scientific works to the field of scholarly publication, this paper [1] has now been retracted and shall be marked accordingly. The authors agree to this retraction. We apologize to our readership that this went undetected until now. ,