Involvement of MAF1homolog, negative regulator of RNA polymeraseIII in colorectal cancer progression.

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, its contribution to cancer progression has 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.