LncRNA‐PVT1 promotes pancreatic cancer cells proliferation and migration through acting as a molecular sponge to regulate miR‐448

Abstract

The identification and characterization of long non-coding RNAs (lncRNAs) in diverse biological process has currently developed rapidly. LncRNA-PVT1, located adjacent to the MYC locus on chromosomal region 8q24, has been reported to be associated with many biological processes. However, the function and mechanism of PVT1 in pancreatic carcinoma (PC) is poorly understood. In this present study, we first measured the level of PVT1 in the PC cell lines and tissues by quantitative real-time PCR (qRT-PCR), and then employed loss-of-function and gain-of-function approaches to explore the association between PVT1 expression levels and PC cell proliferation/migration ability. Furthermore, bioinformatics analysis was utilized to show that PVT1 contains binding site for miR-448 and an inverse correlation between PVT1 and miR-448 was obtained in PC specimens. Additionally, dual luciferase reporter assay, RNA-binding protein immunoprecipitation (RIP) and applied biotin-avidin pulldown system were applied to further confirm that PVT1 directly bind with microRNA binding site harboring in the PVT1 sequence. Then, SERBP1 was identified as a target of miR-448 according to the gene expression array analysis of PC clinical samples. Together, we revealed that PVT1 functions as an endogenous "sponge" by competing for miR-448 binding to regulate the miRNA target SERBP1 and, therefore, promotes the proliferation and migration of PC cells.

Suppression of TLR4 by miR-448 is involved in Diabetic development via regulating Macrophage polarization

“…Another important finding of this study was that miR‐448 was critically related to the LPS‐induced M1 polarization of macrophages. As small, non‐protein coding RNA, miR‐448 played an essential role in cellular functions, including proliferation, migration, and apoptosis through regulating the expression of targeted mRNAs . MiR‐448 was recently found to reduce in peripheral blood of T2D patients after laparoscopic bariatric surgery and overexpressed miR‐448 suppressed the viability and invasion of circulating endothelial progenitor cells through targeting SIRT1 .…”

“…As small, non-protein coding RNA, miR-448 played an essential role in cellular functions, including proliferation, migration, and apoptosis through regulating the expression of targeted mRNAs. [34,35] MiR-448 was recently found to reduce in peripheral blood of T2D patients after laparoscopic bariatric surgery and overexpressed miR-448 suppressed the viability and invasion of circulating endothelial progenitor cells through targeting SIRT1. [36] In contrast to TLR4, our data showed that miR-448 was significantly decreased in T2D mice-derived macrophages.…”

TGF‐β‐mediated exosomal lnc‐MMP2‐2 regulates migration and invasion of lung cancer cells to the vasculature by promoting MMP2 expression

“…Noncoding RNAs encoded by the eukaryotic genome comprise a large number of RNAs that are not translated into proteins. Accumulating evidence revealed major transcriptional and posttranscriptional regulatory roles of long noncoding (lnc)RNAs and include transcription‐factor recruitment, chromatin remodeling, histone modification, pre‐mRNA splicing, and as molecular sponges and scaffolds involved in the development of normal tissues or organs, as well as in carcinogenesis and the aggression of diverse malignancies …”

“…Accumulating evidence revealed major transcriptional and posttranscriptional regulatory roles of long noncoding (lnc)RNAs 16 and include transcription-factor recruitment, chromatin remodeling, histone modification, pre-mRNA splicing, and as molecular sponges and scaffolds involved in the development of normal tissues or organs, as well as in carcinogenesis and the aggression of diverse malignancies. 17,18 A previous study reported that TGF-β influences microRNA (miRNA) expression in exosomes 19 ; however, the role of TGF-β in promoting exosomal lncRNA expression has not been reported. Here, we performed coculture of TGF-β-treated A549 cells with lung cancer cells or lung microvascular endothelial cells to evaluate the TGF-β-mediated invasion ability of the lung cancer cells and changes in permeability of the vascular endothelial cell layer.…”

Interactions between short and long noncoding RNAs

“…Most of these studies are performed in cancer cell lines. For example, as of March 2018, there are at least 17 studies reporting ceRNA activity of PVT1 [70][71][72][73][74][75][76][77][78][79][80][81][82][83][84][85][86], a moderately abundant lncRNA, that is almost exclusively nuclear [87,88], and therefore not expected to effectively bind miRNAs. Strikingly, these studies collectively implicate 10 different miRNAs as being 'sponged' by PVT1.…”