HNRNP A1 Promotes Lung Cancer Cell Proliferation by Modulating VRK1 Translation.

Abstract

THeterogeneous nuclear ribonucleoprotein (HNRNP) A1 is the most abundant and ubiquitously expressed member of the HNRNP protein family. In recent years, it has become more evident that HNRNP A1 contributes to the development of neurodegenerative diseases. However, little is known about the underlying role of HNRNP A1 in cancer development. Here, we report that HNRNP A1 expression is significantly increased in lung cancer tissues and is negatively correlated with the overall survival of patients with lung cancer. Additionally, HNRNP A1 positively regulates vaccinia-related kinase 1 (VRK1) translation via binding directly to the 3' untranslated region (UTR) of VRK1 mRNA, thus increasing cyclin D1 (CCND1) expression by VRK1-mediated phosphorylation of the cAMP response element-binding protein (CREB). Furthermore, HNRNP A1 binding to the cis-acting region of the 3'UTR of VRK1 mRNA contributes to increased lung cancer cell proliferation. Thus, our study unveils a novel role of HNRNP A1 in lung carcinogenesis via post-transcriptional regulation of VRK1 expression and suggests its potential as a therapeutic target for patients with lung cancer.

• Authors: Hye Guk Ryu, Youngseob Jung, Namgyu Lee, Ji-Young Seo, Sung Wook Kim, Kyung-Ha Lee, Do-Yeon Kim, Kyong-Tai Kim
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 22 Issue 11 (May 23 2021) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 34071140 (Publication Type: Journal Article)

Chemical References

• 3' Untranslated Regions
• CCND1 protein, human
• EIF3B protein, human
• Eukaryotic Initiation Factor-3
• Heterogeneous Nuclear Ribonucleoprotein A1
• Intracellular Signaling Peptides and Proteins
• Neoplasm Proteins
• RNA, Messenger
• Recombinant Proteins
• hnRNPA1 protein, human
• Cyclin D1
• Protein Serine-Threonine Kinases
• VRK1 protein, human

Topics

• 3' Untranslated Regions
• Base Sequence
• CRISPR-Cas Systems
• Cell Cycle
• Cell Line
• Cyclin D1 (biosynthesis, genetics)
• Eukaryotic Initiation Factor-3 (metabolism)
• Gene Expression Regulation, Neoplastic
• Genes, Reporter
• Heterogeneous Nuclear Ribonucleoprotein A1 (chemistry, physiology)
• Humans
• Intracellular Signaling Peptides and Proteins (biosynthesis, genetics)
• Lung Neoplasms (genetics, pathology)
• Neoplasm Proteins (biosynthesis, chemistry, genetics, physiology)
• Protein Binding
• Protein Biosynthesis
• Protein Domains
• Protein Interaction Mapping
• Protein Serine-Threonine Kinases (biosynthesis, genetics)
• RNA Interference
• RNA, Messenger (genetics, metabolism)
• Recombinant Proteins (metabolism)
• Sequence Deletion
• Up-Regulation