HNRNP A1 Promotes Lung Cancer Cell Proliferation by Modulating VRK1 Translation

Hye Guk Ryu; Youngseob Jung; Namgyu Lee; Ji-Young Seo; Sung Wook Kim; Kyung-Ha Lee; Do-Yeon Kim; Kyong-Tai Kim

doi:10.3390/ijms22115506

HNRNP A1 Promotes Lung Cancer Cell Proliferation by Modulating VRK1 Translation

Int J Mol Sci. 2021 May 23;22(11):5506. doi: 10.3390/ijms22115506.

Authors

Hye Guk Ryu¹, Youngseob Jung², Namgyu Lee³, Ji-Young Seo², Sung Wook Kim², Kyung-Ha Lee⁴, Do-Yeon Kim⁵, Kyong-Tai Kim^{1

2}

Affiliations

¹ Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang 37673, Korea.
² Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology (POSTECH), Pohang 37673, Korea.
³ Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA 01065, USA.
⁴ Division of Cosmetic Science and Technology, Daegu Haany University, Gyeongsan 38610, Korea.
⁵ Department of Pharmacology, School of Dentistry, Kyungpook National University, Daegu 41940, Korea.

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.

Keywords: 3′UTR; HNRNP A1; VRK1; lung cancer; post-transcriptional regulation.

MeSH terms

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

Substances

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