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 language | English |
|---|---|
| Pages (from-to) | 1001-1009 |
| Number of pages | 9 |
| Journal | International journal of oncology |
| Volume | 54 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - Mar 2019 |
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All Science Journal Classification (ASJC) codes
- Oncology
- Cancer Research
Cite this
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 journal › Article
}
TY - JOUR
T1 - Involvement of MAF1 homolog, negative regulator of RNA polymerase III in colorectal cancer progression
AU - Hokonohara, Kentaro
AU - Nishida, Naohiro
AU - Miyoshi, Norikatsu
AU - Takahashi, Hidekazu
AU - Haraguchi, Naotsugu
AU - Hata, Taishi
AU - Matsuda, Chu
AU - Mizushima, Tsunekazu
AU - Doki, Yuichiro
AU - Mori, Masaki
PY - 2019/3
Y1 - 2019/3
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=85060637242&partnerID=8YFLogxK
U2 - 10.3892/ijo.2019.4678
DO - 10.3892/ijo.2019.4678
M3 - Article
C2 - 30628658
AN - SCOPUS:85060637242
VL - 54
SP - 1001
EP - 1009
JO - International Journal of Oncology
JF - International Journal of Oncology
SN - 1019-6439
IS - 3
ER -