Expression of both poly r(C) binding protein 1 (PCBP1) and miRNA-3978 is suppressed in peritoneal gastric cancer metastasis

Abstract

The expression of legumain which has been shown overexpressed in patients with metastatic gastric cancer is positively correlated to both disease progression and outcome, and negatively correlated to microRNA (miR)−3978 expression. The RNA-binding protein, poly r(C) binding protein 1 (PCBP1) was the most downregulated protein in the metastatic tissue specimens. Quantitative real-time PCR showed that PCBP1 expression is transcriptionally downregulated in peritoneal metastasis tissues. RNA immunoprecipitation experiments showed that PCBP1 and miR-3978 are sequestered in normal peritoneal tissue, but the complex is disrupted following metastatic progression. PCBP1 expression mimicked miR-3978 expression across gastric cancer patients. Finally, replenishment of PCBP1 or miR-3978 expression in the peritoneal metastasis cell line MKN45 decreased legumain protein expression and chemosensitized the cells to treatment with docetaxel. However, replenishment of one and concomitant depletion of the other failed to induce chemosensitivity to docetaxel. Replenishment of miR-3978 also resulted in induction of PCBP1 protein expression, potentially indicating that miR-3978 expression might downregulate a negative regulator targeting PCBP1. Our current study reveals PCBP1 as an additional biomarker in peritoneal metastasis. PCBP1 and miR-3978 expression were correlated and suggests a potential interplay of differential miRNA biogenesis and RNA binding protein during metastatic progression.

The role and robustness of the Gini coefficient as an unbiased tool for the selection of Gini genes for normalising expression profiling data

“…When we selected the top 20 expressing genes in each data set, only 13 of these were common across these data sets; Table 3 shows some descriptive statistics of 13 of these, with descriptive statistics of all 115 genes found in Supplementary Table S1. Of these genes, two (HNRNPK and PCBP1) are GiniGenes and one (SLC25A3) is a gene previously reported by Caracausi et al Seven out of the 13 genes (HNRNPK, HNRNPC, PCBPB, SF3B1, SRSF3, EDF1 and EIF4H) here share important roles in RNA transcription, translation and stability [92-100], are implicated in a number of diseases, including cancer [92, 95, 101-111], and some, such as SRSF3 are essential for embryo development [112]. Given their pivotal functions, it may be unsurprising that the expression of these genes are tightly regulated across cell lines of different tissue origins, even where these are cancer cell lines.…”

Diverse roles of RNA‐binding proteins in cancer traits and their implications in gastrointestinal cancers

“…Many other RBPs also exhibit changed expression in GC tissues. The hnRNP‐A1, ‐A2/B1, ‐C, ‐F, ‐K, polypyrimidine tract‐binding protein (PTBP)‐1, ‐3, poly r(C) binding protein 2, IMP‐3, Musashi‐1, and non‐POU domain containing octamer binding protein (NONO) were upregulated (C. Chen et al, ; Huang et al, ; Jing et al, ; P. T. Lee et al, ; D. Li et al, ; Park et al, ; Shou et al, ; Sugiyama et al, ; S. H. Xu et al, ; R. Yang et al, ; Zhou et al, ), while RNA‐binding motif (RBM)‐4, ‐5, RBM single‐stranded interacting protein 3 (RBMS3), and PCBP1 were inhibited (Ji et al, ; Kobayashi et al, ; Y. Wu et al, ; Yong et al, ; T. Zhang et al, ). These aberrant expression patterns were thought to associate with pathologic feature and survival of GC patients, but further investigations are needed to reveal their functions and direct targets during cancer development.…”

Overexpression of splicing factor poly(rC)-binding protein 1 elicits cycle arrest, apoptosis induction, and p73 splicing in human cervical carcinoma cells

“…PCBP1 is an evolutionarily conserved RNA-binding protein that regulates transcription, translation, and alternative splicing of genes [3,15,16]. Increasing evidence revealed that PCBP1 is significantly downregulated in gastric cancer [4], acute myeloid leukemia [5], non-small-cell lung cancer [6], and cervical cancer [7] et al and is involved in tumor metastasis. Subsequently, scientists pointed out that PCBP1 might act as a tumor suppressor in various tumors [17,18].…”

“…In recent years, researches focus on the relationship between PCBP1 and tumors. Studies have been found that PCBP1 acts as a tumor suppressor in tumors and the expression is significantly downregulated in various tumors, including gastric cancer [4], acute myeloid leukemia [5], non-small-cell lung cancer [6], cervical cancer [7] et al In general, PCBP1 plays a multifunctional role in tumor progress. For instance, PCBP1 has an influence on apoptosis in variety cancers [8,9].…”