<p>lncRNA PCBP1-AS1 Aggravates the Progression of Hepatocellular Carcinoma via Regulating PCBP1/PRL-3/AKT Pathway</p>

Abstract

Background Hepatocellular carcinoma (HCC) is a very belligerent primary liver tumor with high metastatic potential. Aberrant expression of lncRNAs drives tumorous invasion and metastasis. Whether lncRNAs engage mechanisms of liver cancer metastasis remains largely unexplored. Patients and Methods We collected HCC tissues from the tumors and their adjacent normal samples in the Chinese population and analyzed the levels of lncRNAs by microarray analysis. The gain- and loss-of-function analysis demonstrated that PCBP1-AS1 accelerated tumorous growth and metastasis in vivo and in vitro. Moreover, we used RNA-pulldown assay to show that PCBP1-AS1 physically interacted with polyC-RNA-binding protein 1 (PCBP1); meanwhile, PCBP1-AS1 was indeed detected in RIP with the PCBP1 antibody. Mechanistically, we first explored the relationship between PCBP1‐AS1 and PCBP1 in HCC cell lines. Results Here we show that PCBP1-AS1, identified by microarray analysis on pre- and post-operative HCC plasma specimens, was highly expressed in human HCC, clinically verified as a prometastatic factor and markedly associated with poor prognosis in patients with hepatocellular carcinoma. PCBP1‐AS1 was negatively related with PCBP1 at the messenger RNA and protein expression levels. PCBP1-AS1 triggered PRL-3 and AKT in HCC tumor cells. Additionally, the double knockout of PCBP1 and PCBP1-AS1 abolished the PCBP1-AS1-induced PRL-3-AKT signalling pathway activation. Conclusion The upregulation of PCBP1-AS1 enhances proliferation and metastasis in HCC, thus regulating the PCBP1-PRL-3-AKT signalling pathway.

LncRNA PCBP1-AS1-mediated AR/AR-V7 deubiquitination enhances prostate cancer enzalutamide resistance

“…Most of this research identified PCBP1-AS1 as a biomarker or a factor in ceRNA networks. Till present, PCBP1-AS1 was identified to be functional or a biomarker in hepatocellular cancer, oral carcinoma, and Hodgkin lymphoma [ 21 – 23 ]. However, these studies are not in-depth.…”

“…In this research, PCBP1-AS1 are usually identified by bioinformatics or high-throughput sequencing, and only a few phenotypic experiments are used to confirm its functions, and its mechanisms and possible clinical application values have not been discussed in-depth. However, it is worth noting that in hepatocellular carcinoma, the relevant mechanism of PCBP1-AS1 has been reported [ 23 ]. In this study, PCBP1-AS1 was reported to promote the progression of hepatocellular carcinoma by interacting with PCBP1 to regulate the PRL-3/AKT signaling pathway.…”

Knockdown of lncRNA LINC01234 Suppresses the Tumorigenesis of Liver Cancer via Sponging miR-513a-5p

“…Moreover, miRNAs have been considered as important biological regulators for multiple diseases, including liver cancer (1,17). Meanwhile, in previous studies, lncRNAs have been reported to mediate the tumorigenesis of liver cancer via sponging miRNAs (15,18). For example, Hong et al (19) found that lncRNA LINC00460 can contribute to tumor growth and metastasis of hepatocellular carcinoma through miR-342-3pdependent AGR2 up-regulation.…”

Genome-wide CRISPR interference screen identifies long non-coding RNA loci required for differentiation and pluripotency

“…We found that while 6 lncRNA hits clustered with mRNAs ( VLDLR-AS1, PCBP-AS1, LAMTOR5-AS1, HOXC-AS1, LINC00623 , and FOXD3-AS1 ), the majority of our lncRNA hits did not ( Figure 6D ). Moreover, for each of these 6 lncRNAs, there is experimental evidence for an RNA-based phenotype, either through lncRNA knockdown approaches ( VLDLR-AS1 and LAMTOR5-AS1 ) (Chen et al 2019, Takahashi et al 2014; Li et al, 2020) or, in 4 cases ( HOXC-AS1, FOXD3-AS1, PCBP-AS1 and LINC00623 ), also including lncRNA ectopic overexpression approaches (Huang et al, 2016; Lu et al, 2013; Zhao et al, 2018; Luo et al, 2020; Yan et al, 2017).…”