Details

Autor(en) / Beteiligte

• Sun, Kangyue
• Chen, Lu
• Li, Yiwen
• Huang, Bing
• Yan, Qun
• Wu, Changjie
• Lai, Qiuhua
• Fang, Yuxin
• Cai, Jianqun
• Liu, Yongfeng
• Chen, Junsheng
• Wang, Xinke
• Zhu, Yuxuan
• Dong, Shuyu
• Tan, Jieyu
• Li, Aimin
• Liu, Side
• Zhang, Yue

Titel

METTL14-dependent maturation of pri-miR-17 regulates mitochondrial homeostasis and induces chemoresistance in colorectal cancer

Ist Teil von

• Cell death & disease, 2023-02, Vol.14 (2), p.148-148, Article 148

Ort / Verlag

England: Springer Nature B.V

Erscheinungsjahr

2023

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• miR-17-5p has been found to be involved in the proliferation and metastasis of colorectal cancer (CRC), and N -methyladenosine (m A) modification is the most common RNA modification in eukaryotes. However, whether miR-17-5p contributes to chemotherapy sensitivity in CRC via m A modification is unclear. In this study, we found that overexpression of miR-17-5p led to less apoptosis and lower drug sensitivity in vitro and in vivo under the 5-fluorouracil (5-FU) treatment, which indicated miR-17-5p led to 5-FU chemotherapy resistance. Bioinformatic analysis suggested that miR-17-5p-mediated chemoresistance was associated with mitochondrial homeostasis. miR-17-5p directly bound to the 3' untranslated region of Mitofusin 2 (MFN2), leading to decreased mitochondrial fusion and enhanced mitochondrial fission and mitophagy. Meanwhile, methyltransferase-like protein 14 (METTL14) was downregulated in CRC, resulting in lower m A level. Moreover, the low level of METTL14 promoted the expression of pri-miR-17 and miR-17-5p. Further experiments suggested that m A mRNA methylation initiated by METTL14 inhibits pri-miR-17 mRNA decay via reducing the recognition of YTHDC2 to the "GGACC" binding site. The METTL14/miR-17-5p/MFN2 signaling axis may play a critical role in 5-FU chemoresistance in CRC.