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Involved microRNAs in alternative polyadenylation intervene in breast cancer via regulation of cleavage factor “CFIm25”
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Involved microRNAs in alternative polyadenylation intervene in breast cancer via regulation of cleavage factor “CFIm25”
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Journal Article
Involved microRNAs in alternative polyadenylation intervene in breast cancer via regulation of cleavage factor “CFIm25”
2020
Overview
Cleavage factor “CFIm25”, as a key repressor at proximal poly (A) site, negatively correlates to cell proliferation and tumorigenicity in various cancers. Hence, understanding CFIm25 mechanism of action in breast cancer would be a great benefit. To this aim four steps were designed. First, potential
miRNAs
that target 3′-UTR of
CFIm25
mRNA, retrieved from Targetscan web server. Second, screened
miRNAs
were profiled in 100 breast cancer and 100 normal adjacent samples. Third,
miRNAs
that their expression was inversely correlated to the CFIm25, overexpressed in MDA-MB-231 cell line, and their effect on proliferation and migration monitored via MTT and wound healing assays, respectively. Fourth, interaction of
miRNAs
of interest with 3′-UTR of
CFIm25
confirmed via luciferase assay and western blot. Our results indicate that
CFIm25
considerably down-regulates in human breast cancer tissue. qRT-PCR assay, luciferase test, and western blotting confirm that
CFIm25
itself could be directly regulated by oncomiRs such as
miR-23
,
-24, -27, -135, -182
and
-374
. Besides, according to MTT and wound healing assays of cell lines,
CFIm25
knockdown intensifies cell growth, proliferation and migration. Our results also confirm indirect impact of CFIm25 on regulation of mRNA’s 3′–UTR length, which then control corresponding
miRNAs’
action.
miRNAs
directly control CFIm25 expression level, which then tunes expression of the oncogenes and tumor proliferation. Therefore, regulation of CFIm25 expression level via
miRNAs
is expected to improve treatment responses in breast cancer.
Publisher
Nature Publishing Group UK,Nature Publishing Group
