Heterogenous Nuclear Ribonucleoprotein H1 Promotes Colorectal Cancer Progression through the Stabilization of mRNA of Sphingosine-1-Phosphate Lyase 1
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 s...
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| Format: | Article |
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MDPI AG
2020-06-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/12/4514 |
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| author | Keitaro Takahashi Mikihiro Fujiya Hiroaki Konishi Yuki Murakami Takuya Iwama Takahiro Sasaki Takehito Kunogi Aki Sakatani Katsuyoshi Ando Nobuhiro Ueno Shin Kashima Kentaro Moriichi Hiroki Tanabe Toshikatsu Okumura |
| author_facet | Keitaro Takahashi Mikihiro Fujiya Hiroaki Konishi Yuki Murakami Takuya Iwama Takahiro Sasaki Takehito Kunogi Aki Sakatani Katsuyoshi Ando Nobuhiro Ueno Shin Kashima Kentaro Moriichi Hiroki Tanabe Toshikatsu Okumura |
| author_sort | Keitaro Takahashi |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T18:53:34Z |
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| language | English |
| last_indexed | 2024-03-10T18:53:34Z |
| publishDate | 2020-06-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-af1a9c26b1e74a84a0ae43a7c191ecb82023-11-20T04:56:04ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-06-012112451410.3390/ijms21124514Heterogenous Nuclear Ribonucleoprotein H1 Promotes Colorectal Cancer Progression through the Stabilization of mRNA of Sphingosine-1-Phosphate Lyase 1Keitaro Takahashi0Mikihiro Fujiya1Hiroaki Konishi2Yuki Murakami3Takuya Iwama4Takahiro Sasaki5Takehito Kunogi6Aki Sakatani7Katsuyoshi Ando8Nobuhiro Ueno9Shin Kashima10Kentaro Moriichi11Hiroki Tanabe12Toshikatsu Okumura13Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, 2-1 Midorigaoka-higashi, Asahikawa, Hokkaido 078-8510, JapanDivision of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, 2-1 Midorigaoka-higashi, Asahikawa, Hokkaido 078-8510, JapanDepartment of Gastroenterology and Advanced Medical Sciences, Asahikawa Medical University, 2-1 Midorigaoka-higashi, Asahikawa, Hokkaido 078-8510, JapanDivision of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, 2-1 Midorigaoka-higashi, Asahikawa, Hokkaido 078-8510, JapanDivision of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, 2-1 Midorigaoka-higashi, Asahikawa, Hokkaido 078-8510, JapanDivision of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, 2-1 Midorigaoka-higashi, Asahikawa, Hokkaido 078-8510, JapanDivision of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, 2-1 Midorigaoka-higashi, Asahikawa, Hokkaido 078-8510, JapanDivision of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, 2-1 Midorigaoka-higashi, Asahikawa, Hokkaido 078-8510, JapanDivision of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, 2-1 Midorigaoka-higashi, Asahikawa, Hokkaido 078-8510, JapanDivision of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, 2-1 Midorigaoka-higashi, Asahikawa, Hokkaido 078-8510, JapanDivision of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, 2-1 Midorigaoka-higashi, Asahikawa, Hokkaido 078-8510, JapanDivision of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, 2-1 Midorigaoka-higashi, Asahikawa, Hokkaido 078-8510, JapanDivision of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, 2-1 Midorigaoka-higashi, Asahikawa, Hokkaido 078-8510, JapanDivision of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, 2-1 Midorigaoka-higashi, Asahikawa, Hokkaido 078-8510, JapanThe 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.https://www.mdpi.com/1422-0067/21/12/4514hnRNP H1SGPL1S1PRNA-binding proteincolorectal cancer |
| spellingShingle | Keitaro Takahashi Mikihiro Fujiya Hiroaki Konishi Yuki Murakami Takuya Iwama Takahiro Sasaki Takehito Kunogi Aki Sakatani Katsuyoshi Ando Nobuhiro Ueno Shin Kashima Kentaro Moriichi Hiroki Tanabe Toshikatsu Okumura Heterogenous Nuclear Ribonucleoprotein H1 Promotes Colorectal Cancer Progression through the Stabilization of mRNA of Sphingosine-1-Phosphate Lyase 1 International Journal of Molecular Sciences hnRNP H1 SGPL1 S1P RNA-binding protein colorectal cancer |
| title | Heterogenous Nuclear Ribonucleoprotein H1 Promotes Colorectal Cancer Progression through the Stabilization of mRNA of Sphingosine-1-Phosphate Lyase 1 |
| title_full | Heterogenous Nuclear Ribonucleoprotein H1 Promotes Colorectal Cancer Progression through the Stabilization of mRNA of Sphingosine-1-Phosphate Lyase 1 |
| title_fullStr | Heterogenous Nuclear Ribonucleoprotein H1 Promotes Colorectal Cancer Progression through the Stabilization of mRNA of Sphingosine-1-Phosphate Lyase 1 |
| title_full_unstemmed | Heterogenous Nuclear Ribonucleoprotein H1 Promotes Colorectal Cancer Progression through the Stabilization of mRNA of Sphingosine-1-Phosphate Lyase 1 |
| title_short | Heterogenous Nuclear Ribonucleoprotein H1 Promotes Colorectal Cancer Progression through the Stabilization of mRNA of Sphingosine-1-Phosphate Lyase 1 |
| title_sort | heterogenous nuclear ribonucleoprotein h1 promotes colorectal cancer progression through the stabilization of mrna of sphingosine 1 phosphate lyase 1 |
| topic | hnRNP H1 SGPL1 S1P RNA-binding protein colorectal cancer |
| url | https://www.mdpi.com/1422-0067/21/12/4514 |
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