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.

中文翻译：

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RPF2 介导 CARM1-MYCN 轴以促进结直肠癌细胞的化疗耐药性。

核糖体生产因子2同源物（RPF2）在核糖体生物合成的生命过程中发挥着重要作用；然而RPF2在肿瘤中的功能和机制尚不清楚。本研究表明 RPF2 表达与结直肠癌 (CRC) 细胞的化疗耐药有关。目前的研究表明，CRC中RPF2表达的上调促进了CRC细胞对化疗药物的耐药性，而RPF2的敲低则导致CRC对化疗的敏感性增加。此外，还发现RPF2的过度表达导致CRC细胞中ATP结合盒（ABC）B1表达增加；因此，抑制RPF2会降低CRC细胞中ABCB1的水平，从而表明ABCB1可能是RPF2的下游因子，促进CRC化疗耐药。结果还表明，CRC 细胞中 ABCB1 的上游调节因子 N-myc 原癌基因蛋白 (MYCN) 的表达受到 RPF2 的影响。此外，还发现RPF2的下游蛋白共激活剂相关精氨酸甲基转移酶1（CARM1）存在与MYCN的直接结合，并且这种相互作用受到RPF2的调节。上述结果提示RPF2可能通过CARM1-MYCN通路调节CRC中ABCB1的表达，从而促进CRC耐药。