<scp>METTL3</scp>‐induced <scp>FGD5‐AS1</scp> contributes to the tumorigenesis and <scp>PD‐1</scp>/<scp>PD‐L1</scp> checkpoint to enhance the resistance to paclitaxel of endometrial carcinoma
Min Hao, Tianjie Li, Ling Xiao, Yun Liu
Abstract
Endometrial 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.