Zeng Juan, Zhang Heying, Tan Yonggang, Wang Zhe, Li Yunwei, Yang Xianghong
Department of Oncology, Shengjing Hospital of China Medical University, Shenyang Liaoning 110004, China.
Department of Pathology, Shengjing Hospital of China Medical University, Shenyang Liaoning 110004, China.
Mol Ther Nucleic Acids. 2021 Jun 24;25:277-292. doi: 10.1016/j.omtn.2021.06.005. eCollection 2021 Sep 3.
Pancreatic cancer is the deadliest malignancy of the digestive system and is the seventh most common cause of cancer-related deaths worldwide. The incidence and mortality of pancreatic cancer continue to increase, and its 5-year survival rate remains the lowest among all cancers. N6-methyladenine (m6A) is the most abundant reversible RNA modification in various eukaryotic messenger and long noncoding RNAs and plays crucial roles in the occurrence and development of cancers. However, the role of m6A in pancreatic cancer remains unclear. The present study aimed to explore the role of m6A and its regulators in pancreatic cancer and assess its underlying molecular mechanism associated with pancreatic cancer cell proliferation, invasion, and metastasis. Reduced expression of the m6A demethylase, fat mass and obesity-associated protein (FTO), was responsible for the high levels of m6A RNA modification in pancreatic cancer. Moreover, FTO demethylated the m6A modification of (), thereby reducing its mRNA decay, suppressing Wnt signaling, and ultimately restraining the proliferation, invasion, and metastasis of pancreatic cancer cells. Altogether, this study describes new, potential molecular therapeutic targets for pancreatic cancer that could pave the way to improve patient outcome.
胰腺癌是消化系统最致命的恶性肿瘤，是全球癌症相关死亡的第七大常见原因。胰腺癌的发病率和死亡率持续上升，其5年生存率在所有癌症中仍然是最低的。N6-甲基腺嘌呤（m6A）是各种真核生物信使RNA和长链非编码RNA中最丰富的可逆RNA修饰，在癌症的发生和发展中起关键作用。然而，m6A在胰腺癌中的作用仍不清楚。本研究旨在探讨m6A及其调节因子在胰腺癌中的作用，并评估其与胰腺癌细胞增殖、侵袭和转移相关的潜在分子机制。m6A去甲基化酶、脂肪量和肥胖相关蛋白（FTO）的表达降低是胰腺癌中m6A RNA修饰水平升高的原因。此外，FTO使（）的m6A修饰去甲基化，从而减少其mRNA降解，抑制Wnt信号传导，并最终抑制胰腺癌细胞的增殖、侵袭和转移。总之，本研究描述了胰腺癌新的潜在分子治疗靶点，这可能为改善患者预后铺平道路。
