LncRNA SNHG1 and RNA binding protein hnRNPL form a complex and coregulate CDH1 to boost the growth and metastasis of prostate cancer

Abstract

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.

5-Methylcytosine RNA Methyltransferases-Related Long Non-coding RNA to Develop and Validate Biochemical Recurrence Signature in Prostate Cancer

“…For example, the lncRNA HOTAIR has been found highly expressed in primary breast tumors and metastases, promoting cancer progression ( Gupta et al, 2010 ), while Second Chromosome Locus Associated with Prostate-1, LINC00913 , tends to be a promising biomarker given that its expression level is independently related to poor prognosis ( Prensner et al, 2013 ). In our previous study, SNHG1 has also been proved to be a novel lncRNA, contributing to the malignant progression in PCa ( Tan et al, 2021 ). Previously, methylation of 5-cytosine at the post-transcriptional level was found only in tRNAs and rRNAs.…”

NBPF4 mitigates progression in colorectal cancer through the regulation of EZH2‐associated ETFA

“…45 Recently, the involvement of RBPs in gene expression and its regulation by lncRNAs has been revealed. 46,47 qRT-PCR results, we identified that both NBPF4 and EZH2 are bound and regulated by RNA binding protein ZFP36. ZFP36 is an RBP associated with tumorigenesis and is involved in transcription regulation and RNA processing.…”

“…Further, RBPs are also considered to be important regulators in gene expression 45 . Recently, the involvement of RBPs in gene expression and its regulation by lncRNAs has been revealed 46,47 . For example, overexpression of ZFP36 can reverse the upregulation of EZH2 caused by shNBPF4 and vice versa.…”

“… 45 Recently, the involvement of RBPs in gene expression and its regulation by lncRNAs has been revealed. 46 , 47 For example, overexpression of ZFP36 can reverse the upregulation of EZH2 caused by shNBPF4 and vice versa. Furthermore, when we explored the commonalities between them from RNA immunoprecipitation and qRT‐PCR results, we identified that both NBPF4 and EZH2 are bound and regulated by RNA binding protein ZFP36.…”

Evolution of the Neocortex Through RNA-Binding Proteins and Post-transcriptional Regulation

“…Celf1 acts as a Cdh1 repressor and Elavl1 acts as a translational derepressor ( Yu et al, 2016 ). A recent study in human prostate cancer cells implicated another RBP, hnRNPL, in the post-transcriptional regulation of Cdh1 via modulation of Cdh1 transcript stability ( Tan et al, 2021 ). Interestingly, Elavl1 directly interacts with hnRNPL in rat hepatocytes to stabilize inducible nitric oxide synthase transcripts in response to inflammatory stimuli ( Matsui et al, 2008 ).…”