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Article

Heterogenous Nuclear Ribonucleoprotein H1 Promotes Colorectal Cancer Progression through the Stabilization of mRNA of Sphingosine-1-Phosphate Lyase 1

1
Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, 2-1 Midorigaoka-higashi, Asahikawa, Hokkaido 078-8510, Japan
2
Department of Gastroenterology and Advanced Medical Sciences, Asahikawa Medical University, 2-1 Midorigaoka-higashi, Asahikawa, Hokkaido 078-8510, Japan
3
Department of Medicine, Knapp Center for Biomedical Discovery, The University of Chicago, 900 East 57th Street, 9th floor, Chicago, IL 60637, USA
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2020, 21(12), 4514; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21124514
Received: 29 March 2020 / Revised: 18 June 2020 / Accepted: 23 June 2020 / Published: 25 June 2020
(This article belongs to the Special Issue Pathophysiology in Colonic Diseases)
The oncogenic properties of heterogeneous nuclear ribonucleoprotein H1 (hnRNP H1) have been reported, although the tumor-promoting mechanism remains unclear. We herein report the mechanism underlying colorectal cancer cell progression mediated by hnRNP H1. The growth of colorectal cancer cells was suppressed by hnRNP H1 downregulation. A terminal deoxynucleotidyl transferase dUTP nick-end labeling assay revealed the anti-apoptotic effect of hnRNP H1 in colorectal cancer cells. An RNA immunoprecipitation assay revealed that hnRNP H1 bound to sphingosine-1-phosphate lyase 1 (SGPL1). Reverse transcription-polymerase chain reaction revealed the high expression of hnRNP H1 mRNA in colorectal cancer cells and Spearman’s rank correlation coefficient showed a strong positive correlation between hnRNP H1 mRNA and SGPL1 mRNA. An siRNA of hnRNP H1 decreased SGPL1 mRNA expression in colorectal cancer cells, but not in non-tumorous cells. These findings suggested that hnRNP H1 increased SGPL1 mRNA expression specifically in cancer cells through direct binding. Targeted knockdown of hnRNP H1 or SGPL1 with siRNAs upregulated p53 phosphorylation and p53-associated molecules, resulting in cell growth inhibition, while hnRNP H1 upregulated the mRNA of SGPL1 and inhibited p53 activation, thereby promoting tumor cell growth. This is a novel mechanism underlying colorectal cancer cell progression mediated by hnRNP H1–SGPL1 mRNA stabilization. View Full-Text
Keywords: hnRNP H1; SGPL1; S1P; RNA-binding protein; colorectal cancer hnRNP H1; SGPL1; S1P; RNA-binding protein; colorectal cancer
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MDPI and ACS Style

Takahashi, K.; Fujiya, M.; Konishi, H.; Murakami, Y.; Iwama, T.; Sasaki, T.; Kunogi, T.; Sakatani, A.; Ando, K.; Ueno, N.; Kashima, S.; Moriichi, K.; Tanabe, H.; Okumura, T. Heterogenous Nuclear Ribonucleoprotein H1 Promotes Colorectal Cancer Progression through the Stabilization of mRNA of Sphingosine-1-Phosphate Lyase 1. Int. J. Mol. Sci. 2020, 21, 4514. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21124514

AMA Style

Takahashi K, Fujiya M, Konishi H, Murakami Y, Iwama T, Sasaki T, Kunogi T, Sakatani A, Ando K, Ueno N, Kashima S, Moriichi K, Tanabe H, Okumura T. Heterogenous Nuclear Ribonucleoprotein H1 Promotes Colorectal Cancer Progression through the Stabilization of mRNA of Sphingosine-1-Phosphate Lyase 1. International Journal of Molecular Sciences. 2020; 21(12):4514. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21124514

Chicago/Turabian Style

Takahashi, Keitaro, Mikihiro Fujiya, Hiroaki Konishi, Yuki Murakami, Takuya Iwama, Takahiro Sasaki, Takehito Kunogi, Aki Sakatani, Katsuyoshi Ando, Nobuhiro Ueno, Shin Kashima, Kentaro Moriichi, Hiroki Tanabe, and Toshikatsu Okumura. 2020. "Heterogenous Nuclear Ribonucleoprotein H1 Promotes Colorectal Cancer Progression through the Stabilization of mRNA of Sphingosine-1-Phosphate Lyase 1" International Journal of Molecular Sciences 21, no. 12: 4514. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21124514

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