Related Experiment Video

Updated: May 2, 2026

Using the E1A Minigene Tool to Study mRNA Splicing Changes
10:25

Using the E1A Minigene Tool to Study mRNA Splicing Changes

Published on: April 22, 2021

4.5K

Splicing factor hnRNP A2 activates the Ras-MAPK-ERK pathway by controlling A-Raf splicing in hepatocellular carcinoma

Asaf Shilo, Vered Ben Hur, Polina Denichenko

    RNA (New York, N.Y.)
    |February 28, 2014
    PubMed

    Insights

    Increased levels of heterogeneous nuclear ribonucleoprotein A1/A1b (hnRNP A1) and hnRNP A2/B1 (hnRNP A2) promote hepatocellular carcinoma (HCC) development by altering A-Raf splicing and activating the Ras-MAPK-ERK pathway.

    Area of Science:

    • Molecular Biology
    • Oncology
    • Cancer Research

    Background:

    • Splicing factors are increasingly recognized for their role in cancer development.
    • Previous work identified SRSF1, SRSF6, and hnRNP A2/B1 as oncogenes in various cancers.
    • The specific roles of hnRNP A1/A1b and hnRNP A2/B1 in hepatocellular carcinoma (HCC) require further investigation.

    Purpose of the Study:

    • To investigate the role of splicing factors hnRNP A1/A1b and hnRNP A2/B1 in hepatocellular carcinoma (HCC).
    • To elucidate the molecular mechanisms by which these splicing factors contribute to HCC progression.

    Main Methods:

    • Analysis of hnRNP A1 and hnRNP A2 expression in an inflammation-induced liver cancer mouse model.
    • Overexpression and knockdown studies in immortalized liver progenitor cells and human liver cancer cell lines.
    • Investigation of the Ras-MAPK-ERK pathway activation and A-Raf splicing.
    • Assessment of anchorage-independent growth and tumor growth inhibition.

    Main Results:

    • hnRNP A1 and hnRNP A2 were found to be up-regulated in HCC tumors from the mouse model.
    • Overexpression of hnRNP A1 or hnRNP A2 induced tumor formation, while their knockdown inhibited growth.
    • hnRNP A2 overexpression constitutively activated the Ras-MAPK-ERK pathway.
    • hnRNP A2 knockdown inhibited the Ras-MAPK-ERK pathway and ERK1/2 activation.
    • hnRNP A2 was shown to regulate A-Raf splicing, decreasing a dominant-negative isoform and increasing the full-length transcript.

    Conclusions:

    • Up-regulation of hnRNP A2 in HCC drives an alternative splicing switch in A-Raf.
    • This splicing alteration leads to the activation of the Raf-MEK-ERK pathway.
    • The activated pathway promotes cellular transformation and tumor development in HCC.
    Keywords:
    A-RafMAPKRNA processingalternative splicinghnRNP A2/B1liver cancer

    More Related Videos

    Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods07:49

    Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods

    Published on: July 17, 2019

    5.7K
    Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants07:38

    Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants

    Published on: June 6, 2025

    951

    Related Concept Videos

    MAPK Signaling Cascades01:07

    MAPK Signaling Cascades

    Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
    7.3K
    The Ras Gene02:38

    The Ras Gene

    The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
    Ras is a...
    5.7K
    RNA Splicing01:32

    RNA Splicing

    Splicing is the process by which eukaryotic RNA is edited before its translation into protein. The RNA strand transcribed from eukaryotic DNA is called the primary transcript. The primary transcripts that become mRNAs are called precursor messenger RNAs (pre-mRNAs). Eukaryotic pre-mRNA contains alternating sequences of exons and introns. Exons are nucleotide sequences that code for proteins, whereas introns are the non-coding regions. In RNA splicing, introns are removed and exons are bonded...
    53.3K
    RNA Splicing01:32

    RNA Splicing

    15.9K
    Interactions Between Signaling Pathways01:19

    Interactions Between Signaling Pathways

    Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
    Convergence and divergence, and cross-talk between signaling pathways
    Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
    4.7K
    Alternative RNA Splicing02:18

    Alternative RNA Splicing

    Alternative RNA splicing is the regulated splicing of exons and introns to produce different mature mRNAs from a single pre-mRNA. Unlike in constitutive splicing where a single gene produces a single type of mRNA, alternative splicing allows an organism to produce multiple proteins from a single gene and plays an important role in protein diversity.
    There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
    20.5K