Involvement of MAF1�homolog, negative regulator of RNA polymerase�III 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.

Maf1 suppression of ATF5-dependent mitochondrial unfolded protein response contributes to rapamycin-induced radio-sensitivity in lung cancer cell line A549

“…Maf1 siRNA (5’-GGCUCAAGCGAAUCGUCUUTT-3’) and ATF5 siRNA (5’-GTCCAAATCATGAAATGTTTG-3’) published before [ 20 , 48 ]. For transient knockdown, cells were transfected with siRNA using siRNA-Mate transfection reagent (Genepharma) according to manufacturer’s instruction.…”

“…Maf1 is an mTORC1 effector that has significant roles in cancer biology [ 20 – 24 ]. Maf1 is phosphorylated by mTORC1 at certain Serine and Threonine to regulate RNA Polymerase III-dependent transcription of tRNAs, microRNAs and other small nuclear RNAs [ 7 , 25 , 26 ].…”

Pan-cancer driver copy number alterations identified by joint expression/CNA data analysis

“… 19 ASH2L 42 ARMC1 ARMC1, YTHDF3, TCEA1, UBE2W, IMPAD1, ARFGEF1, STAU2, RB1CC1, LYPLA1, VCPIP1, RAB2A 8q13.1 Neither Breast cancer 43 and thyroid cancer 44 YTHDF3 45 UTP23 UTP23, FAM91A1, RAD21, MTDH, TAF2, ATP6V1C1, AZIN1, OTUD6B, SLC25A32, VIRMA 8q24.11 Neither Breast cancer 43 , 46 and non-small cell lung cancer 47 RAD21 48 SHARPIN SHARPIN, CYHR1, HSF1, VPS28, BOP1, HGH1, EXOSC4, COMMD5, ZC3H3, DGAT1, ADCK5, MAF1, FBXL6, PUF60, SLC52A2, PPP1R16A, PYCR3, GPAA1, GLI4, LRRC14 8q24.3 Refs. 18 , 19 SHARPIN 49 , MAF1 50 YME1L1 YME1L1, KIF5B, WAC, ABI1, RAB18, ACBD5 10p12.1 Neither Diffuse Large B-Cell Lymphoma 51 RAB18 52 MED21 MED21, MRPS35, ERGIC2, INTS13, FGFR1OP2 12p11.23 Ref. 18 ERGIC2 53 CLTC CLTC, INTS2, MED13, APPBP2, BPTF, HELZ, DCAF7, CCDC47 17q23.1 Refs.…”

Plasma Exosomal miRNA Expression Profile as Oxaliplatin-Based Chemoresistant Biomarkers in Colorectal Adenocarcinoma

“…Interestingly, our results showed that the regulation of transcription from the RNA polymerase II promoter may be associated with one of the most prominent differences in chemoresistance in CRC. Researchers have found that RNA polymerase could modulate drug resistance and cancer progression in CRC ( 45 , 46 ), but the specific mechanism of RNA polymerase II in chemoresistance should be explored in the future. The PI3K-Akt signaling and MAPK signaling pathways are important in the maintenance of cancer stem cells, which can mediate therapy resistance by dormancy, increased DNA repair, drug efflux, and so on ( 21 ).…”