Involvement of MAF1 homolog, negative regulator of RNA polymerase III in colorectal cancer progression

Kentaro Hokonohara, Naohiro Nishida, Norikatsu Miyoshi, Hidekazu Takahashi, Naotsugu Haraguchi, Taishi Hata, Chu Matsuda, Tsunekazu Mizushima, Yuichiro Doki, Masaki Mori

Research output: Contribution to journalArticle

Abstract

Polymerase (Pol) III-dependent transcription controls the abundance of transfer RNAs, 5S ribosomal RNA and small non-coding RNAs within cells, and is known to serve an essential role in the maintenance of intracellular homeostasis.However,itscontributiontocancerprogressionhas not been extensively explored. The present study demonstrated that the evolutionarily conserved MAF1 homolog, negative regulator of RNA Pol III (MAF1) may be closely associated with malignant potential and poor prognosis in colorectal cancer (CRC). Notably, immunohistochemical analysis of 146 CRC surgical specimens revealed that high expression levels of MAF1 were associated with advanced tumor depth, lymph node metastasis, distant metastasis and poor prognosis. In vitro loss-of-function assays revealed that MAF1 knockdown suppressed chemoresistance and migration of CRC cancer cells. Furthermore, detailed analysis of an independent CRC dataset (n=615) demonstrated that the prognostic impact of MAF1 gene expression was particularly marked in microsatellite instability (MSI)‑positive patients, who benefit from immune checkpoint blockade. High expression levels of MAF1 were revealed to be an independent prognostic indicator in MSI‑positive CRC. These findings suggested that MAF1 may have an essential role in CRC progression, particularly in MSI-positive cases.

Original languageEnglish
Pages (from-to)1001-1009
Number of pages9
JournalInternational journal of oncology
Volume54
Issue number3
DOIs
Publication statusPublished - Mar 2019

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RNA Polymerase III
Colorectal Neoplasms
Microsatellite Instability
5S Ribosomal RNA
Neoplasm Metastasis
Small Untranslated RNA
Transfer RNA
Neoplasms
Homeostasis
Lymph Nodes
Maintenance
Gene Expression

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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Involvement of MAF1 homolog, negative regulator of RNA polymerase III in colorectal cancer progression. / Hokonohara, Kentaro; Nishida, Naohiro; Miyoshi, Norikatsu; Takahashi, Hidekazu; Haraguchi, Naotsugu; Hata, Taishi; Matsuda, Chu; Mizushima, Tsunekazu; Doki, Yuichiro; Mori, Masaki.

In: International journal of oncology, Vol. 54, No. 3, 03.2019, p. 1001-1009.

Research output: Contribution to journalArticle

Hokonohara, K, Nishida, N, Miyoshi, N, Takahashi, H, Haraguchi, N, Hata, T, Matsuda, C, Mizushima, T, Doki, Y & Mori, M 2019, 'Involvement of MAF1 homolog, negative regulator of RNA polymerase III in colorectal cancer progression', International journal of oncology, vol. 54, no. 3, pp. 1001-1009. https://doi.org/10.3892/ijo.2019.4678
Hokonohara, Kentaro ; Nishida, Naohiro ; Miyoshi, Norikatsu ; Takahashi, Hidekazu ; Haraguchi, Naotsugu ; Hata, Taishi ; Matsuda, Chu ; Mizushima, Tsunekazu ; Doki, Yuichiro ; Mori, Masaki. / Involvement of MAF1 homolog, negative regulator of RNA polymerase III in colorectal cancer progression. In: International journal of oncology. 2019 ; Vol. 54, No. 3. pp. 1001-1009.
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