Cytoplasmic overexpression of RNA-binding protein HuR is a marker of poor prognosis in meningioma, and HuR knockdown decreases meningioma cell growth and resistance to hypoxia

RNA-binding proteins have been associated with cancer development. The overexpression of a well-known RNA-binding protein, insulin-like growth factor 2 messenger RNA–binding protein 3, has been identified as an indicator of poor prognosis in patients with various types of cancer. Although gastric cancer is a relatively frequent and potentially fatal malignancy, the mechanism by which insulin-like growth factor 2 messenger RNA–binding protein 3 regulates the development of this cancer remains unclear. This study aimed to investigate the role and regulatory mechanism of insulin-like growth factor 2 messenger RNA–binding protein 3 in gastric cancer. An analysis of IGF2BP3 expression patterns reported in 4 public gastric cancer–related microarray data sets from the Gene Expression Omnibus and The Cancer Genome Atlas-Stomach Adenocarcinoma revealed strong expression of this gene in gastric cancer tissues. Insulin-like growth factor 2 messenger RNA–binding protein 3 expression in gastric cancer was further confirmed via quantitative reverse transcription polymerase chain reaction and immunohistochemistry, respectively, in an in-house gastric cancer cohort (n = 30), and the association of insulin-like growth factor 2 messenger RNA–binding protein 3 expression with clinical parameters and prognosis was analyzed. Notably, stronger IGF2BP3 expression significantly correlated with poor prognosis, and significant changes in insulin-like growth factor 2 messenger RNA–binding protein 3 expression were only confirmed in patients with advanced-stage gastric cancer in an independent cohort. The effects of insulin-like growth factor 2 messenger RNA–binding protein 3 on cell proliferation were confirmed through in vitro experiments involving the HGC-27 gastric cancer cell line. MicroR-125a-5p, a candidate microRNA that target on insulin-like growth factor 2 messenger RNA–binding protein 3, decreased in advanced-stage gastric cancer. Upregulation of microR-125a-5p inhibited insulin-like growth factor 2 messenger RNA–binding protein 3, and dual-luciferase report assay indicated that microR-125a-5p inhibited the translation of IGF2BP3 by directly targeting the 3′ untranslated region. These results indicate that the microR-125a-5p/insulin-like growth factor 2 messenger RNA–binding protein 3 axis contributes to the oncogenesis of advanced gastric cancer.

Download Full-text

Effect of proline rich domain of an RNA-binding protein Sam68 in cell growth process, death and B cell signal transduction

Chinese Medical Journal ◽

10.1097/00029330-200609020-00006 ◽

2006 ◽

Vol 119 (18) ◽

pp. 1536-1542 ◽

Cited By ~ 2

Author(s):

Qing-hua LI ◽

Tian-xue FAN ◽

Tian-xiang PANG ◽

Wen-su YUAN ◽

Zhong-chao HAN

Keyword(s):

Signal Transduction ◽

Cell Growth ◽

B Cell ◽

Growth Process ◽

Rna Binding ◽

Binding Protein ◽

Rna Binding Protein ◽

Cell Signal ◽

Rich Domain ◽

Cell Signal Transduction

Download Full-text

The RNA‐binding protein Musashi 1 stabilizes the oncotachykinin 1 mRNA in breast cancer cells to promote cell growth

The FASEB Journal ◽

10.1096/fj.15-278770 ◽

2015 ◽

Vol 30 (1) ◽

pp. 149-159 ◽

Cited By ~ 14

Author(s):

George R. Nahas ◽

Raghav G. Murthy ◽

Shyam A. Patel ◽

Teja Ganta ◽

Steven J. Greco ◽

...

Keyword(s):

Breast Cancer ◽

Cell Growth ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Rna Binding ◽

Binding Protein ◽

Rna Binding Protein

Download Full-text

AU-rich RNA binding proteins in hematopoiesis and leukemogenesis

Blood ◽

10.1182/blood-2011-07-347237 ◽

2011 ◽

Vol 118 (22) ◽

pp. 5732-5740 ◽

Cited By ~ 35

Author(s):

Maria Baou ◽

John D. Norton ◽

John J. Murphy

Keyword(s):

Cell Growth ◽

Regulatory Networks ◽

Binding Proteins ◽

Rna Binding ◽

Rna Binding Proteins ◽

Binding Protein ◽

Rna Binding Protein ◽

Growth And Survival ◽

Hematopoietic Malignancies ◽

Gene Regulatory

Abstract Posttranscriptional mechanisms are now widely acknowledged to play a central role in orchestrating gene-regulatory networks in hematopoietic cell growth, differentiation, and tumorigenesis. Although much attention has focused on microRNAs as regulators of mRNA stability/translation, recent data have highlighted the role of several diverse classes of AU-rich RNA-binding protein in the regulation of mRNA decay/stabilization. AU-rich elements are found in the 3′-untranslated region of many mRNAs that encode regulators of cell growth and survival, such as cytokines and onco/tumor-suppressor proteins. These are targeted by a burgeoning number of different RNA-binding proteins. Three distinct types of AU-rich RNA binding protein (ARE poly-U–binding degradation factor-1/AUF1, Hu antigen/HuR/HuA/ELAVL1, and the tristetraprolin/ZFP36 family of proteins) are essential for normal hematopoiesis. Together with 2 further AU-rich RNA-binding proteins, nucleolin and KHSRP/KSRP, the functions of these proteins are intimately associated with pathways that are dysregulated in various hematopoietic malignancies. Significantly, all of these AU-rich RNA-binding proteins function via an interconnected network that is integrated with microRNA functions. Studies of these diverse types of RNA binding protein are providing novel insight into gene-regulatory mechanisms in hematopoiesis in addition to offering new opportunities for developing mechanism-based targeted therapeutics in leukemia and lymphoma.

Download Full-text

LncRNA KCNK15-AS1 inhibits pancreatic cancer progression by promoting the expression of its binding protein ACTR3B

10.21203/rs.3.rs-55282/v1 ◽

2020 ◽

Author(s):

Pengfei Wu ◽

Hao Yuan ◽

Xiangya Ding ◽

Qun Chen ◽

Wanli Ge ◽

...

Keyword(s):

Mass Spectrometry ◽

Pancreatic Cancer ◽

Cell Growth ◽

Cyclin D1 ◽

Cell Lines ◽

Rna Binding ◽

Rna Binding Proteins ◽

Binding Protein ◽

Rna Binding Protein ◽

Luciferase Reporter

Abstract Background LncRNAs are reported to play an essential role in multiple tumors, including pancreatic cancer. LncRNAs could impact tumor growth via RNA-binding proteins, working as a coactivators of transcription factors or impacting their gene expression via posttranscriptional regulation. Our study aimed to elucidate the function and mechanism of lncRNA KCNK15-AS1 and its binding protein ACTR3B in PC progression. Our previous data indicated that KCNK15-AS1 is downregulated in PC tissues and cell lines compared to normal controls. Methods In this study, we overexpressed KCNK15-AS1 and ACTR3B in both BxPC-3 and Mia-PaCa-2 cells to detect the cellular phenotype in vitro and in vivo. RNA pulldown assays, mass spectrometry assays and RNA-binding protein immunoprecipitation assays were used to verify KCNK15-AS1 RNA binding protein ACTR3B. Luciferase reporter assay and ubiquitination assay were proceeded to detect the mechanism KCNK15-AS1 upregulated ACTR3B expression. Results Our results showed that overexpression of KCNK15-AS1 significantly inhibited the proliferation, colony formation and migration of PC cells. ACTR3B was screened by RNA pulldown and mass spectrometry assays. RNA-binding protein immunoprecipitation assays confirmed that KCNK15-AS1 physically bound to ACTR3B. Furthermore, mechanistic analyses demonstrated that KCNK15-AS1 promoted ACTR3B expression by inhibiting ACTR3B ubiquitin-mediated degradation and enhancing its promoter activity. Additionally, ACTR3B presented low expression in PC tissues and cell lines, and PC cell growth was significantly repressed when ACTR3B was overexpressed. Moreover, knockdown of ACTR3B in KCNK15-AS1-overexpressing cells reversed the effects of KCNK15-AS1 on PC cell growth via the cyclin D1/CDK4 axis. Conclusion Briefly, our study indicated that the lncRNA KCNK15-AS1/ACTR3B/cyclin D1/CDK4 axis may inhibit PC progression, which provides a potential therapeutic target for PC.

Download Full-text

miR-31 Reduces Cell Growth of Papillary Thyroid Carcinoma by RNA-Binding Protein HuR

Clinical Laboratory ◽

10.7754/clin.lab.2015.150404 ◽

2015 ◽

Vol 61 (11/2015) ◽

Cited By ~ 6

Author(s):

Danping Wu ◽

Bo Wang ◽

Jiangfeng Shang ◽

Jia Song ◽

Hongdan Zhang

Keyword(s):

Papillary Thyroid Carcinoma ◽

Cell Growth ◽

Thyroid Carcinoma ◽

Rna Binding ◽

Binding Protein ◽

Rna Binding Protein ◽

Papillary Thyroid

Download Full-text

Natural product (−)-gossypol inhibits colon cancer cell growth by targeting RNA-binding protein Musashi-1

Molecular Oncology ◽

10.1016/j.molonc.2015.03.014 ◽

2015 ◽

Vol 9 (7) ◽

pp. 1406-1420 ◽

Cited By ~ 66

Author(s):

Lan Lan ◽

Carl Appelman ◽

Amber R. Smith ◽

Jia Yu ◽

Sarah Larsen ◽

...

Keyword(s):

Colon Cancer ◽

Cell Growth ◽

Natural Product ◽

Cancer Cell ◽

Rna Binding ◽

Binding Protein ◽

Rna Binding Protein ◽

Colon Cancer Cell ◽

Cancer Cell Growth

Download Full-text

LncRNA MACC1-AS1 sponges multiple miRNAs and RNA-binding protein PTBP1

Oncogenesis ◽

10.1038/s41389-019-0182-7 ◽

2019 ◽

Vol 8 (12) ◽

Cited By ~ 6

Author(s):

Xiaona Zhang ◽

Yanchun Zhou ◽

Shaoying Chen ◽

Wei Li ◽

Weibing Chen ◽

...

Keyword(s):

Cell Growth ◽

Noncoding Rna ◽

Rna Binding ◽

Binding Protein ◽

Rna Binding Protein ◽

Underlying Mechanism ◽

Regulate Gene Expression ◽

Regulate Cell Growth ◽

Tumor Progress ◽

A Cell

AbstractLong noncoding RNA (lncRNA) represents a class of endogenous RNAs that regulate gene expression in eukaryotes. To date, the function and underlying mechanism of the majority of mammalian lncRNAs remain unknown. Here, we report that MACC1-AS1, a cognate antisense lncRNA of the sixth intron of the MACC1 gene, functions as a cell growth modulator and enhances breast tumor progress. RNA pulldown and luciferase assays showed that MACC1-AS1 contained binding sites for multiple miRNAs, including well-known tumor suppressors miR-384 and miR-145-3p that repress the expression of pleiotrophin (PTN) and c-Myc mRNAs. Binding of miR-384 and miR-145-3p miRNAs to MACC1-AS1 alters the cell growth phenotype through increased expression of PTN and c-Myc mRNAs. MACC1-AS1 also competitively interacted with PTBP1, an RNA-binding protein, via a conserved pyrimidine rich motif within this lncRNA. Binding of PTBP1to MACC1-AS1 not only stabilized MACC1-AS1 and enhanced the sponge effect of MACC1-AS1 on miRNAs, but also decreased PTBP1 availability for binding to target mRNAs. Our results define a new dimension into how a lncRNA is able to regulate cell growth by sponging multiple miRNAs and an RNA-binding protein.

Download Full-text