Molecular Pathogenesis of Colorectal Cancer: Impact of Oncogenic Targets Regulated by Tumor Suppressive miR-139-3p
We recently determined the RNA sequencing-based microRNA (miRNA) expression signature of colorectal cancer (CRC). Analysis of the signature showed that the expression of both strands of pre- ( , the guide strand, and , the passenger strand) was significantly reduced in CRC tissues. Transient transfe...
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Published in | International journal of molecular sciences Vol. 23; no. 19; p. 11616 |
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Main Authors | , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Switzerland
MDPI AG
01.10.2022
MDPI |
Subjects | |
Online Access | Get full text |
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Summary: | We recently determined the RNA sequencing-based microRNA (miRNA) expression signature of colorectal cancer (CRC). Analysis of the signature showed that the expression of both strands of pre-
(
, the guide strand, and
, the passenger strand) was significantly reduced in CRC tissues. Transient transfection assays revealed that expression of
blocked cancer cell malignant transformation (e.g., cell proliferation, migration, and invasion). Notably, expression of
markedly blocked RAC-alpha serine/threonine-protein kinase (AKT) phosphorylation in CRC cells. A combination of in silico database and gene expression analyses of
-transfected cells revealed 29 putative targets regulated by
in CRC cells. RNA immunoprecipitation analysis using an Argonaute2 (AGO2) antibody revealed that
was efficiently incorporated into the RNA-induced silencing complex. Aberrant expression of Keratin 80 (
) was detected in CRC clinical specimens by immunostaining. A knockdown assay using small interfering RNA (siRNA) targeting
showed that reducing
expression suppressed the malignant transformation (cancer cell migration and invasion) of CRC cells. Importantly, inhibiting
expression reduced AKT phosphorylation in CRC cells. Moreover, hexokinase-2 (HK2) expression was reduced in cells transfected with the
siRNAs or
. The involvement of miRNA passenger strands (e.g.,
) in CRC cells is a new concept in miRNA studies. Our tumor-suppressive miRNA-based approach helps elucidate the molecular pathogenesis of CRC. |
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ISSN: | 1422-0067 1661-6596 1422-0067 |
DOI: | 10.3390/ijms231911616 |