文献类型：期刊文献

英文题名：YTHDF2 promotes gastric cancer progression and enhances chemoradiotherapy resistance

作者：Yang, Jian[1,2];Chen, Yawen[3];He, Yang[3];Da, Mingxu[1,2]

第一作者：Yang, Jian

通信作者：Da, M[1]

机构：[1]Lanzhou Univ, Clin Med Coll 1, 222 Tianshui South Rd, Lanzhou 730000, Peoples R China;[2]Gansu Prov Hosp, Dept Surg Oncol, Lanzhou, Peoples R China;[3]Gansu Univ Chinese Med, Lanzhou, Peoples R China

第一机构：Lanzhou Univ, Clin Med Coll 1, 222 Tianshui South Rd, Lanzhou 730000, Peoples R China

通信机构：[1]corresponding author), Lanzhou Univ, Clin Med Coll 1, 222 Tianshui South Rd, Lanzhou 730000, Peoples R China.

年份：2024

卷号：85

期号：2

外文期刊名：DRUG DEVELOPMENT RESEARCH

收录：;Scopus(收录号：2-s2.0-85190466201);WOS:【SCI-EXPANDED(收录号:WOS:001202293600001)】；

基金：This work was supported by the National Natural Science Foundation of China (No: 82160588), the Gansu Natural Science Foundation (No: 21JR1RA016) and the Gansu Youth Natural Science Foundation (No: 21JR7RA645, No: 21JR7RA646).

语种：英文

外文关键词：chemotherapy; CyclinD1; gastric cancer; HIF-1 alpha; proliferation; radiotherapy; YTHDF2

摘要：The role of YTHDF2 in gastric cancer (GC) is controversial. Due to the limitations of technical difficulty and experimental period, research on completely knocking out YTHDF2 is rare. Therefore, further investigations are still needed to clarify the YTHDF2's clinical significance and biological function in GC. To carry out the investigation, an analysis was performed on the expression levels of YTHDF2 in both publicly available databases and samples obtained from patients with gastric cancer. Based on the complete knockout of YTHDF2 using the CRISPR-Cas9 system, in vivo and in vitro experiments were conducted to analyze the effects of YTHDF2 on tumor formation, radiotherapy and chemoradiotherapy resistance in GC. Our investigation revealed an increase in YTHDF2 levels in GC tissues, which was found to be associated with a negative prognosis. Under hypoxic conditions, high expression of YTHDF2 enhanced the invasion of gastric cancer cells, and high expression of YTHDF2 was associated with HIF-1a. YTHDF2 facilitated gastric cancer cell growth in vitro and in vivo. Moreover, the results of the present study demonstrated that YTHDF2 mediated the expression of CyclinD1 and stability of CyclinD1 mRNA. CyclinD1 knockdown inhibited YTHDF2-mediated GC cell proliferation whereas CyclinD1 overexpression ameliorated YTHDF2 knockdown-induced inhibition of GC progression. Furthermore, YTHDF2 also promoted resistance to DDP and CTX chemotherapy, along with radiotherapy treatment for GC cells. The findings suggested that YTHDF2 expression accelerated GC progression through a potential mechanism involving CyclinD1 expression, and enhanced chemoradiotherapy resistance. This indicated that YTHDF2 could be a promising prognostic biomarker and therapeutic target for individuals diagnosed with GC.