RPF2 mediates the CARM1‑MYCN axis to promote chemotherapy resistance in colorectal cancer cells

RPF2 介导 CARM1‑MYCN 轴促进结直肠癌细胞化疗耐药性

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作者:Macheng Lu #, Xingqian Hu #, Cong Cheng, Yuan Zhang, Longchang Huang, Xiangpeng Kong, Zengyao Li, Qiuhua Zhang, Ye Zhang

Abstract

Ribosome production factor 2 homolog (RPF2) plays an important role in the life processes of ribosomal biogenesis; however, the function and mechanism of RPF2 in tumors are unclear. The present study demonstrated that RPF2 expression is involved in chemoresistance in colorectal cancer (CRC) cells. The current study demonstrated that upregulation of RPF2 expression in CRC promoted resistance to chemotherapeutic agents in CRC cells, whereas knockdown of RPF2 leads to increased sensitivity of CRC to chemotherapy. In addition, it was found that overexpression of RPF2 led to an increase in ATP‑binding cassette (ABC)B1 expression in CRC cells; accordingly, inhibition of RPF2 reduced the level of ABCB1 in CRC cells, thus suggesting that ABCB1 may be a downstream factor of RPF2 in the promotion of chemotherapy resistance to CRC. The results also suggested that the expression of N‑myc proto‑oncogene protein (MYCN), an upstream regulator of ABCB1, was affected by RPF2 in CRC cells. In addition, it was also found that the downstream protein coactivator‑associated arginine methyltransferase 1 (CARM1) of RPF2 existed in direct binding to MYCN and this interaction was regulated by RPF2. The above results suggested that RPF2 is probably regulated ABCB1 expression in CRC through the CARM1‑MYCN pathway, thereby promoting CRC drug resistance.

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