RNA-binding proteins in tumor progression

Qin, Hai; Ni, Haiwei; Liu, Yichen; Yang, Yuchong; Xi, Tao; Li, Xiaoman; Zheng, Lufeng

doi:10.1186/s13045-020-00927-w

Cited by 164 publications

(105 citation statements)

References 237 publications

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“…HuR is an RNA binding protein that regulates the stability and protein translation of cancer-related target mRNAs at the post-transcriptional level, thereby affecting the biological characteristics of cancer. 21,22 Our work reveals that HuR could enhance MDR1 mRNA stability and thus increase MDR1 expression, this is consistent with other studies showing that HuR could bind to MDR1 in nonsmall cell lung cancer cells 23 and colorectal cancer. 14 We wonder whether this HuR/MDR1 axis is a common phenomenon in tumors.…”

Section: Ua Promotes the Cytoplasm-nucleus Translocation Of Hur Andsupporting

confidence: 91%

Ursolic acid reduces Adriamycin resistance of human ovarian cancer cells through promoting the HuR translocation from cytoplasm to nucleus

Luo

Shi

et al. 2020

Environmental Toxicology

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Ursolic acid (UA) has been shown to suppress various tumor progression, however, its roles in Adriamycin resistance of human ovarian cancer (OC) cells are still unclear. This work aims to investigate the effects of UA on the Adriamycin resistance of human OC cells. Here, we constructed Adriamycin‐resistant OC SKOV3‐Adr cells and found that UA attenuated Adriamycin resistance in SKOV3‐Adr cells. Additionally, UA enhanced Adriamycin sensitivity in the parental SKOV3 and another OC cell line A2780 cells. Mechanistic studies showed that HuR mRNA level was similar between SKOV3 and SKOV3‐Adr cells, but the cytoplasmic expression of HuR protein was increased in SKOV3‐Adr cells compared with that in SKOV3 cells, and subsequently enhancing the mRNA stability of multidrug resistance gene 1 (MDR1). Moreover, UA had no effects on HuR expression, but promoted the cytoplasm‐nucleus translocation of HuR protein, decreased MDR1 mRNA stability and thus reduced MDR1 expression. Furthermore, overexpression of MDR1 rescued the effects of UA on Adriamycin resistance and sensitivity. This work reveals a novel HuR/MDR1 axis responsible for UA‐mediated attenuation on Adriamycin resistance in OC cells.

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Section: Ua Promotes the Cytoplasm-nucleus Translocation Of Hur Andsupporting

confidence: 91%

Ursolic acid reduces Adriamycin resistance of human ovarian cancer cells through promoting the HuR translocation from cytoplasm to nucleus

Luo

Shi

et al. 2020

Environmental Toxicology

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“…In addition, there were significant correlations between every two of the RBPs (Supplementary Figure S3), indicating their complicated associations. RBPs were implicated in RNA splicing, polyadenylation, mRNA stability, mRNA localization, and translation (Qin et al, 2020). Here, the dysregulations of RBPs might also contribute to the overexpression of KPNA2 and GRB2 and the underexpression of NRAS at protein level.…”

Section: A C E B D Fmentioning

confidence: 99%

KPNA2-Associated Immune Analyses Highlight the Dysregulation and Prognostic Effects of GRB2, NRAS, and Their RNA-Binding Proteins in Hepatocellular Carcinoma

Zhang

Gao

et al. 2020

Front. Genet.

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Karyopherin α2 (KPNA2) was reported to be overexpressed and have unfavorable prognostic effects in many malignancies including hepatocellular carcinoma (HCC). Although its contributions to inflammatory response were reported in many studies, its specific associations with immune infiltrations and immune pathways during cancer progression were unclear. Here, we aimed to identify new markers for HCC diagnosis and prognosis through KPNA2-associated immune analyses. RNA-seq expression data of HCC datasets were downloaded from The Cancer Genome Atlas and International Cancer Genome Consortium. The gene expressions were counts per million normalized. The infiltrations of 24 kinds of immune cells in the samples were evaluated with ImmuCellAI (Immune Cell Abundance Identifier). The Spearman correlations of the immune infiltrations with KPNA2 expression were investigated, and the specific positive correlation of B-cell infiltration with KPNA2 expression in HCC tumors was identified. Fifteen genes in KEGG (Kyoto Encyclopedia of Genes and Genomes) B-cell receptor signaling pathway presented significant correlations with KPNA2 expression in HCC. Among them, GRB2 and NRAS were indicated to be independent unfavorable prognostic factors for HCC overall survival. Clinical Proteomic Tumor Analysis Consortium HCC dataset was investigated to validate the results at protein level. The upregulation and unfavorable prognostic effects of KPNA2 and GRB2 were confirmed, whereas, unlike its mRNA form, NRAS protein was presented to be downregulated and have favorable prognostic effects. Through receiver operating characteristic curve analysis, the diagnostic potential of the three proteins was shown. The RNA-binding proteins (RBPs) of KPNA2, NRAS, and GRB2, downloaded via The Encyclopedia of RNA Interactomes, were investigated for their clinical significance in HCC at protein level. An eight-RBP signature with independent prognostic value and dysregulations in HCC was identified. All the RBPs were significantly correlated with MKI67 expression and at least one of KPNA2, GRB2, and NRAS at protein level in HCC, indicating Zhang et al. KPNA2-Associated Immune Analyses in HCC Frontiers in Genetics | www.frontiersin.org 2 October 2020 | Volume 11 | Article 593273 their roles in HCC progression and the regulation of the three proteins. We concluded that KPNA2, GRB2, NRAS, and their RBPs might have coordinating roles in HCC immunoregulation and progression. They might be new markers for HCC diagnosis and prognosis predication and new targets for HCC immunotherapy.

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“…Changes in these processes affect the RNA life cycle, generate abnormal protein phenotypes and thus would result in the initiation and progression of tumors [ 62 , 63 ]. So far, more than 2000 RBPs have been identified [ 61 ].…”

Section: Features Of Rbpsmentioning

confidence: 99%

Expression, Regulation and Function of microRNA as Important Players in the Transition of MDS to Secondary AML and Their Cross Talk to RNA-Binding Proteins

Bauer

Vaxevanis

Heimer

et al. 2020

IJMS

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Myelodysplastic syndromes (MDS), heterogeneous diseases of hematopoietic stem cells, exhibit a significant risk of progression to secondary acute myeloid leukemia (sAML) that are typically accompanied by MDS-related changes and therefore significantly differ to de novo acute myeloid leukemia (AML). Within these disorders, the spectrum of cytogenetic alterations and oncogenic mutations, the extent of a predisposing defective osteohematopoietic niche, and the irregularity of the tumor microenvironment is highly diverse. However, the exact underlying pathophysiological mechanisms resulting in hematopoietic failure in patients with MDS and sAML remain elusive. There is recent evidence that the post-transcriptional control of gene expression mediated by microRNAs (miRNAs), long noncoding RNAs, and/or RNA-binding proteins (RBPs) are key components in the pathogenic events of both diseases. In addition, an interplay between RBPs and miRNAs has been postulated in MDS and sAML. Although a plethora of miRNAs is aberrantly expressed in MDS and sAML, their expression pattern significantly depends on the cell type and on the molecular make-up of the sample, including chromosomal alterations and single nucleotide polymorphisms, which also reflects their role in disease progression and prediction. Decreased expression levels of miRNAs or RBPs preventing the maturation or inhibiting translation of genes involved in pathogenesis of both diseases were found. Therefore, this review will summarize the current knowledge regarding the heterogeneity of expression, function, and clinical relevance of miRNAs, its link to molecular abnormalities in MDS and sAML with specific focus on the interplay with RBPs, and the current treatment options. This information might improve the use of miRNAs and/or RBPs as prognostic markers and therapeutic targets for both malignancies.

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RNA-binding proteins in tumor progression

Cited by 164 publications

References 237 publications

Ursolic acid reduces Adriamycin resistance of human ovarian cancer cells through promoting the HuR translocation from cytoplasm to nucleus

Ursolic acid reduces Adriamycin resistance of human ovarian cancer cells through promoting the HuR translocation from cytoplasm to nucleus

KPNA2-Associated Immune Analyses Highlight the Dysregulation and Prognostic Effects of GRB2, NRAS, and Their RNA-Binding Proteins in Hepatocellular Carcinoma

Expression, Regulation and Function of microRNA as Important Players in the Transition of MDS to Secondary AML and Their Cross Talk to RNA-Binding Proteins

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