A novel VHLα isoform inhibits Warburg effect via modulation of PKM splicing

Liu, Yanbin; Hong-yuan, Yang; Lin, Liang-In; Chen, She; Zuo, Feifei; Chen, Liang

doi:10.1007/s13277-016-5191-y

Cited by 3 publications

(9 citation statements)

References 42 publications

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“…These results indicated the important roles of hnRNPA2B1 in mediating the pro-tumoral activities of c-myc, which was under stringent control by VHLα feedback loop. Notably, the greater inhibitory effects of VHLα than hnRNPA2B1specific shRNA suggested the other anti-tumor mechanisms of VHLα such as inhibition of hypoxia induced factor as previously described 18 . The pro-proliferative activities of hnRNPA2B1 was also uncovered by colony formation assay, wherein c-myc overexpression dramatically increased the colony number which was greatly reduced by either hnRNPA2B1 depletion or VHLα-proficiency (representative images and statistical data were provided in Fig.…”

Section: Vhlα Exerted Anti-tumoral Roles Through Negative Control Of supporting

confidence: 67%

“…Our previous study demonstrated that hnRNPA2B1 was significantly decreased by VHLα other than other isoforms, which was blockaded by proteasome inhibitor, MG132, and suggested the involvement of ubiquitination/ proteasome system-mediated protein degradation 18 . We also noticed that MG132 treatment caused increase of VHLα in addition to accumulation of hnRNPA2B1, which implicated the possible feedback regulation on VHLα.…”

Section: Direct Association Between Hnrnpa2b1 and Octadic Pentamer Rementioning

confidence: 94%

“…Our previous study demonstrated that VHLα decreased hnRNPA2B1 at protein level which was efficiently blockaded by proteasome inhibitor, MG132, indicating the potential ubiquitination of hnRNPA2B1 by VHLα 18 . In this study, we set out to further identify the ubiquitination sites of hnRNPA2B1 and critical regions of VHLα responsible for protein interaction.…”

Section: Introductionmentioning

confidence: 90%

“…Our previous study first uncovered the alternative translation of VHL transcript and identified a novel protein isoform named VHLα 18 . However, the alternative translation initiation codon was still to be defined and the molecular mechanism underlying regulation of alternative translation of VHL transcript was largely elusive.…”

Section: Eif2a and Eif4a Involve In Vhlα Alternative Translationmentioning

confidence: 99%

“…Our pervious study uncovered the characteristic perinuclear distribution of VHL-19 complexing with the ribosomal large subunit 6 (RPL6), which may play critical roles in quality control of nascent peptides 17 . In addition, we identified a novel translation variant of VHL as well, termed VHLα, via alternative translation mechanism, which negatively regulates heterogenous nuclear ribonucleoprotein A2B1 (hnRNPA2B1) and therefore modulates pyruvate kinase transcription splicing 18 . However, the initiation site and regulation of VHLα alternative translation are still largely unknown.…”

Section: Introductionmentioning

confidence: 99%

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Identification of anti-tumoral feedback loop between VHLα and hnRNPA2B1 in renal cancer

Liu

Zhang

et al. 2020

Cell Death Dis

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Our previous study identified a novel VHLα isoform which negatively modulated hnRNPA2B1 expression and therefore influenced pyruvate kinase transcript splicing in renal cancer, while the regulation and initiation of alternative translation are largely unknown. Here we unraveled the CUG-mediated translation start of VHLα, which was subjected to the regulation by both eukaryotic initiator factor eIF2A and RNA helicase eIF4A. Unexpectedly, we found hnRNPA2B1 promoted VHLα alternative translation as well via direct interaction with its octadic pentamer region of VHL transcript. The N-terminal of VHLα was indispensable in mediating ubiquitination of hnRNPA2B1 at lysine residues 274 and 305. We further identified aberrant overexpression of c-myc as upstream oncogenic signaling to positively regulate hnRNPA2B1 transcription in renal cancer. Therefore, our data suggested an anti-tumoral feedback loop between VHLα and hnRNPA2B1.

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Section: Vhlα Exerted Anti-tumoral Roles Through Negative Control Of supporting

confidence: 67%

Section: Direct Association Between Hnrnpa2b1 and Octadic Pentamer Rementioning

confidence: 94%

Section: Introductionmentioning

confidence: 90%

Section: Eif2a and Eif4a Involve In Vhlα Alternative Translationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Identification of anti-tumoral feedback loop between VHLα and hnRNPA2B1 in renal cancer

Liu

Zhang

et al. 2020

Cell Death Dis

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Biological function and research progress of N6-methyladenosine binding protein heterogeneous nuclear ribonucleoprotein A2B1 in human cancers

Liu

Chen

et al. 2023

Front. Oncol.

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N6-methyladenosine (m6A) is the most prevalent internal modification found in both mRNA and lncRNA. It exerts reversible regulation over RNA function and affects RNA processing and metabolism in various diseases, especially tumors. The m6A binding protein, hnRNPA2B1, is extensively studied as a member of the heterogeneous nuclear ribonucleoprotein (hnRNP) protein family. It is frequently dysregulated and holds significant importance in multiple types of tumors. By recognizing m6A sites for variable splicing, maintaining RNA stability, and regulating translation and transport, hnRNPA2B1 plays a vital role in various aspects of tumor development, metabolism, and regulation of the immune microenvironment. In this review, we summarized the latest research on the functional roles and underlying molecular mechanisms of hnRNPA2B1. Moreover, we discussed its potential as a target for tumor therapy.

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The Many Roads from Alternative Splicing to Cancer: Molecular Mechanisms Involving Driver Genes

Gimeno-Valiente,

López-Rodas,

Castillo

et al. 2024

Cancers

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Cancer driver genes are either oncogenes or tumour suppressor genes that are classically activated or inactivated, respectively, by driver mutations. Alternative splicing—which produces various mature mRNAs and, eventually, protein variants from a single gene—may also result in driving neoplastic transformation because of the different and often opposed functions of the variants of driver genes. The present review analyses the different alternative splicing events that result in driving neoplastic transformation, with an emphasis on their molecular mechanisms. To do this, we collected a list of 568 gene drivers of cancer and revised the literature to select those involved in the alternative splicing of other genes as well as those in which its pre-mRNA is subject to alternative splicing, with the result, in both cases, of producing an oncogenic isoform. Thirty-one genes fall into the first category, which includes splicing factors and components of the spliceosome and splicing regulators. In the second category, namely that comprising driver genes in which alternative splicing produces the oncogenic isoform, 168 genes were found. Then, we grouped them according to the molecular mechanisms responsible for alternative splicing yielding oncogenic isoforms, namely, mutations in cis splicing-determining elements, other causes involving non-mutated cis elements, changes in splicing factors, and epigenetic and chromatin-related changes. The data given in the present review substantiate the idea that aberrant splicing may regulate the activation of proto-oncogenes or inactivation of tumour suppressor genes and details on the mechanisms involved are given for more than 40 driver genes.

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A novel VHLα isoform inhibits Warburg effect via modulation of PKM splicing

Cited by 3 publications

References 42 publications

Identification of anti-tumoral feedback loop between VHLα and hnRNPA2B1 in renal cancer

Identification of anti-tumoral feedback loop between VHLα and hnRNPA2B1 in renal cancer

Biological function and research progress of N6-methyladenosine binding protein heterogeneous nuclear ribonucleoprotein A2B1 in human cancers

The Many Roads from Alternative Splicing to Cancer: Molecular Mechanisms Involving Driver Genes

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