METTL3‐induced FGD5‐AS1 contributes to the tumorigenesis and PD‐1/PD‐L1 checkpoint to enhance the resistance to paclitaxel of endometrial carcinoma

Abstract

AbstractEndometrial cancer (EC), a widely occurring cancer in the uterus, is among the top four most frequent malignancies in women. To improve approaches for combating this disease, it is essential to gain a more comprehensive comprehension of the intricate causes of EC. Accumulating evidence highlight the essential role of long non‐coding RNA (LncRNA) in EC progression, while its biological and mechanical function has not been fully revealed. In this study, a LncRNA microarray analysis was performed using four pairs of paclitaxel (PTX) resistant EC cells, FGD5‐AS1 was identified as a significantly upregulated gene. Biologically, it was found that FGD5‐AS1 enhances chemoresistance of EC cells to PTX treatment and blocking immune escape via PD‐1/PD‐L1 checkpoint. Furthermore, FGD5‐AS1 exerted an oncogene role in EC cells via promoting cell proliferation and migration. Mechanically, METTL3 could upregulate FGD5‐AS1 expression via N6‐methyladenosine (m6A) modification. The biological roles of METTL3 were exerted via modulating FGD5‐AS1 expression in EC. Collectively, our research has shed light on the involvement of the METTL3/FGD5‐AS1 axis in the development of PTX resistance in EC. This finding offers a new avenue for further exploration of the underlying mechanisms of chemoresistance in EC and provides valuable insights for the development of potential therapeutic targets in the treatment of EC.