LncRNA SNHG1 and RNA binding protein hnRNPL form a complex and coregulate CDH1 to boost the growth and metastasis of prostate cancer
The interaction between LncRNA and RNA-binding protein (RBPs) plays an essential role in the regulation over the malignant progression of tumors. Previous studies on the mechanism of SNHG1 , an emerging lncRNA, have primarily focused on the competing endogenous RNA (ceRNA) mechanism. Nevertheless, t...
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Published in | Cell death & disease Vol. 12; no. 2; p. 138 |
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Main Authors | , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
London
Nature Publishing Group UK
01.02.2021
Springer Nature B.V Nature Publishing Group |
Subjects | |
Online Access | Get full text |
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Summary: | The interaction between LncRNA and RNA-binding protein (RBPs) plays an essential role in the regulation over the malignant progression of tumors. Previous studies on the mechanism of
SNHG1
, an emerging lncRNA, have primarily focused on the competing endogenous RNA (ceRNA) mechanism. Nevertheless, the underlying mechanism between
SNHG1
and RBPs in tumors remains to be explored, especially in prostate cancer (PCa).
SNHG1
expression profiles in PCa were determined through the analysis of TCGA data and tissue microarray at the RNA level. Gain- and loss-of-function experiments were performed to investigate the biological role of
SNHG1
in PCa initiation and progression. RNA-seq, immunoblotting, RNA pull-down and RNA immunoprecipitation analyses were utilized to clarify potential pathways with which
SNHG1
might be involved. Finally, rescue experiments were carried out to further confirm this mechanism. We found that
SNHG1
was dominantly expressed in the nuclei of PCa cells and significantly upregulated in PCa patients. The higher expression level of
SNHG1
was dramatically correlated with tumor metastasis and patient survival. Functionally, overexpression of
SNHG1
in PCa cells induced epithelial–mesenchymal transition (EMT), accompanied by down-regulation of the epithelial marker,
E-cadherin
, and up-regulation of the mesenchymal marker,
vimentin
. Increased proliferation and migration, as well as accelerated xenograft tumor growth, were observed in
SNHG1
-overexpressing PCa cells, while opposite effects were achieved in
SNHG1
-silenced cells. Mechanistically,
SNHG1
competitively interacted with
hnRNPL
to impair the translation of protein
E-cadherin
, thus activating the effect of
SNHG1
on the EMT pathway, eventually promoting the metastasis of PCa. Our findings demonstrate that
SNHG1
is a positive regulator of EMT activation through the
SNHG1
-
hnRNPL
-CDH1 axis.
SNHG1
may serve as a novel potential therapeutic target for PCa. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 2041-4889 2041-4889 |
DOI: | 10.1038/s41419-021-03413-4 |