Department of Oncology, Fudan University Pudong Medical Center, Shanghai Pudong Hospital, 2800 Gongwei Road, Shanghai, 201399, China.
BMC Cancer. 2022 Jun 2;22(1):602. doi: 10.1186/s12885-022-09709-8.
Mucin 3A (MUC3A) is overexpressed in colorectal cancer (CRC) and associated with poor prognosis, but the related mechanism remains unclear. Our study found that MUC3A promotes the progression of CRC by activating the PI3K/Akt/mTOR signaling pathway. Knockout of MUC3A significantly inhibited the proliferation of CRC cells and induced G1 phase arrest by upregulating p21 protein, an important cell cycle regulator. Moreover, knockout of MUC3A significantly inhibited invasion ability and enhanced the sensitivity to the chemotherapeutic agent 5-FU. Furthermore, we found that knockout of MUC3A repressed the PI3K/Akt/mTOR pathway through RNA-seq. Treatment with the PI3K/Akt/mTOR pathway inhibitor rapamycin successfully eliminated the difference in proliferation, invasion and chemoresistance between MUC3A knockout cells and control cells. Our study suggests that MUC3A is a potential oncogene that promotes the proliferation, invasion, and chemotherapy resistance of CRC. Moreover, CRC patients with high expression of MUC3A may benefit from rapamycin treatment.
黏蛋白 3A（MUC3A）在结直肠癌（CRC）中过表达，并与不良预后相关，但相关机制尚不清楚。我们的研究发现，MUC3A 通过激活 PI3K/Akt/mTOR 信号通路促进 CRC 的进展。敲除 MUC3A 可通过上调重要的细胞周期调节剂 p21 蛋白显著抑制 CRC 细胞的增殖并诱导 G1 期阻滞。此外，敲除 MUC3A 可显著抑制侵袭能力并增强对化疗药物 5-FU 的敏感性。此外，我们通过 RNA-seq 发现敲除 MUC3A 可抑制 PI3K/Akt/mTOR 通路。用 PI3K/Akt/mTOR 通路抑制剂雷帕霉素处理可成功消除 MUC3A 敲除细胞与对照细胞之间在增殖、侵袭和化疗耐药性方面的差异。我们的研究表明，MUC3A 是一种潜在的癌基因，可促进 CRC 的增殖、侵袭和化疗耐药性。此外，MUC3A 高表达的 CRC 患者可能受益于雷帕霉素治疗。
