23/08/1402
Targeting long non-coding RNA MALAT1 reverses cancerous phenotypes of breast cancer cells through microRNA-561-3p/TOP2A axis
Non-coding RNAs, including Inc-RNA and miRNA, have been reported to
regulate gene expression and are associated with cancer progression.
MicroRNA-561-3p (miR-561-3p), as a tumor suppressor, has been reported
to play a role in preventing cancer cell progression, and MALAT1
(Lnc-RNA) have also been demonstrated to promote malignancy in various
cancers, such as breast cancer (BC). In this study, we aimed to
determine the correlation between miR-561-3p and MALAT1 and their roles
in breast cancer progression. The expression of MALAT1, mir-561-3p, and
topoisomerase alpha 2 (TOP2A) as a target of miR-561-3p was determined
in BC clinical samples and cell lines via qRT-PCR. The binding site
between MALAT1, miR-561-3p, and TOP2A was investigated by performing the
dual luciferase reporter assay. MALAT1 was knocked down by siRNA, and
cell proliferation, apoptotic assays, and cell cycle arrest were
evaluated. MALAT1 and TOP2A were significantly upregulated, while
mir-561-3p expression was downregulated in BC samples and cell lines.
MALAT1 knockdown significantly increased miR-561-3p expression, which
was meaningfully inverted by co-transfection with the miR 561-3p
inhibitor. Furthermore, the knockdown of MALAT1 by siRNA inhibited
proliferation, induced apoptosis, and arrested the cell cycle at the G1
phase in BC cells. Notably, the mechanistic investigation revealed that
MALAT1 predominantly acted as a competing endogenous RNA in BC by
regulating the miR-561-3p/TOP2A axis. Based on our results, MALAT1
upregulation in BC may function as a tumor promoter in BC via directly
sponging miRNA 561-3p, and MALAT1 knockdown serves a vital antitumor
role in BC cell progression through the miR-561-3p/TOP2A axis.