TITLE:
MIR-448 Regulates MAGEA6/AMPK Signaling Pathway in Hepatocellular Carcinoma Tumor Stem Cells
AUTHORS:
Changliang Jiao, Jinfang Zheng, Juncheng Guo
KEYWORDS:
mir-448, MAGEA6, AMPK Signaling Pathway, Liver Cancer, Tumor Stem Cells
JOURNAL NAME:
Journal of Cancer Therapy,
Vol.14 No.4,
April
28,
2023
ABSTRACT: Objective: To explore the role of miR-448 in regulating MAGEA6/AMPK signaling
pathway in the biological study of hepatocellular carcinoma (HCC) tumor stem
cells. Methods: Using the database, the hepatocellular carcinoma related
expression chips were obtained and the regulatory mirnas of candidate genes
were predicted, and the predicted results were analyzed. The effects of miR-448
and MAGEA6 on the pellet formation rate and clone formation rate of
hepatocellular carcinoma stem cells were detected by immunofluorescence
identification of stem cell markers and light microscope counting method. The
effects of miR-448 and MAGEA6 on migration and invasion of hepatocellular carcinoma stem cells were detected
by scratch and Transwell assay. Dual luciferase reporter assay to verify
whether miR-448 targets MAGEA6. The expression and influence of miR-448
on MAGEA6 and AMPK pathway were detected by qRT-PCR and Western blot. Results: It was found that miR-448 may directly regulate the expression of MAGEA6.
Overexpression of miR-448 inhibited the characteristics, proliferation,
migration, and invasion of hepatocellular carcinoma stem cells in vitro, as well as the ability of
xenograft tumor formation in vivo.
However, inhibition of miR-448 showed opposite results. In addition, miR-448
directly targets MAGEA6 and regulates AMPK
signaling. Silencing MAGEA6 and adding AMPK activator further verified that
miR-448 activated AMPK signaling pathway by targeting MAGEA6, thus
affecting characteristics, proliferation, migration and invasion of hepatoma stem cells. Conclusions: Our results
reveal that miR-448 activates AMPK signaling pathway by targeting
MAGEA6, thereby affecting characteristics, proliferation, migration and
invasion of hepatoma stem cells. It is suggested that overexpression of miR-448
may be a new therapeutic strategy for hepatocellular carcinoma.