Department of Pharmacy, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang 150040, China.
Beidahuang Industry Group General Hospital, Department of Clinical Laboratory, No. 235, Hashuang Road, Nangang District, Harbin, Heilongjiang, China.
Pathol Res Pract. 2024 Jan;253:155047. doi: 10.1016/j.prp.2023.155047. Epub 2023 Dec 21.
Ovarian cancer has the highest mortality among all gynecological malignancies. Therefore, it is urgent to determine the molecular mechanism of ovarian cancer progression. As the most prevalent modification of messenger RNA (mRNA), N6-Methyladenosine (mA) modification is recognized as a key regulatory role in the progression of various tumors. However, the specific role of mA and its related regulatory pathways in ovarian cancer (OV) remains unclear. In this study, we demonstrated that the METTL3/YTHDF1 mA axis plays an important role in the progression of ovarian cancer. Depletion of METTL3/YTHDF1 impaired cancer proliferation and metastasis in vitro and in vivo. Mechanistically, The METTL3/YTHDF1 m6A axis directly binds to the mRNA of DDR2, thereby promoting the expression levels of the tumor promoter DDR2 and thus contributing to the progression of ovarian cancer. Collectively, our findings on the METTL3/YTHDF1/DDR2 mA axis provide the insight into the underlying mechanism of ovarian carcinogenesis and highlight potential therapeutic targets for cancer treatment.
卵巢癌是妇科恶性肿瘤中死亡率最高的癌症。因此，迫切需要确定卵巢癌进展的分子机制。作为信使 RNA（mRNA）最普遍的修饰方式，N6-甲基腺苷（m6A）修饰被认为在各种肿瘤的进展中起着关键的调节作用。然而，m6A 及其相关调控途径在卵巢癌（OV）中的具体作用尚不清楚。在这项研究中，我们证实 METTL3/YTHDF1 m6A 轴在卵巢癌的进展中起着重要作用。METTL3/YTHDF1 的耗竭会损害体外和体内的癌症增殖和转移。在机制上，METTL3/YTHDF1 m6A 轴直接结合 DDR2 的 mRNA，从而促进肿瘤促进因子 DDR2 的表达水平，从而促进卵巢癌的进展。总之，我们对 METTL3/YTHDF1/DDR2 m6A 轴的研究结果为卵巢癌发生的潜在机制提供了深入的了解，并强调了癌症治疗的潜在治疗靶点。
