Dimethyladenosine Transferase 1 Homolog Promotes Human Gastric Carcinoma Cell Proliferation and Inhibits Apoptosis via the AKT Pathway

作者全名："Liu, Guang-yi; Wang, Huan; Ran, Rui; Wang, Yi-cheng; Li, Yang"

作者地址："[Liu, Guang-yi; Ran, Rui; Wang, Yi-cheng; Li, Yang] Chongqing Med Univ, Dept Gastrointestinal Surg, Affiliated Hosp 2, Chongqing, Peoples R China; [Wang, Huan] Chongqing Med Univ, Dept Hlth Management Ctr, Affiliated Hosp 2, Chongqing, Peoples R China"

通信作者："Li, Y (通讯作者)，Chongqing Med Univ, Dept Gastrointestinal Surg, Affiliated Hosp 2, Chongqing, Peoples R China."

来源：TURKISH JOURNAL OF GASTROENTEROLOGY

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:001109157300003

JCR分区：Q4

影响因子：1.4

年份：2023

卷号：34

期号：8

开始页：802

结束页：812

文献类型：Article

关键词：DIMT1; gastric carcinoma; proliferation; apoptosis; gene regulation

摘要："Background/Aims: Our previous work identified the dimethyladenosine transferase 1 homolog as a novel prognostic factor for detecting human gastric carcinoma with high sensitivity and specificity. The high expression of dimethyladenosine transferase 1 is closely associated with the occurrence and progression of gastric carcinoma. However, the underlying mechanism of dimethyladenosine transferase 1 for the occurrence and development of gastric carcinoma is not well elucidated yet. Materials and Methods: In our present study, the biological role of dimethyladenosine transferase 1 on cell proliferation, apoptosis, and cell cycle progression in human gastric carcinoma cells was investigated through in vitro and in vivo assays by the overexpression and knockdown of dimethyladenosine transferase 1 2-way authentication method. Results: We found that the overexpression of dimethyladenosine transferase 1 significantly promotes cell proliferation (P <.001) and inhibition of cell apoptosis (P <.01) in SGC-7901 cells. However, the in vivo experiment results of the knockdown dimethyladenosine transferase 1 using small interfering RNAs in the MKN-45 are just the opposite. Reverse-transcriptase polymerase chain reaction and western blotting analysis revealed that overexpressed dimethyladenosine transferase 1 in SGC-7901 cells significantly activated the AKT pathway compared to control cells. In contrast, we found that apoptosis genes such as Caspase-3 and Caspase-9 were down-regulated in those cells. The xenograft nude mice model exhibited increased tumor growth (P <.01) and weight loss (P <.01), with the overexpression of dimethyladenosine transferase 1 homolog in the SGC-7901 cells. These results have been further confirmed through backward verification in dimethyladenosine transferase 1 knockdown cells. Conclusions: Taken together, our results indicated that the dimethyladenosine transferase 1 plays a crucial role in stimulating cancer cell proliferation and contributes to apoptosis resistance in human gastric carcinoma. Meanwhile, it provides a potential therapeutic target for gastric carcinoma treatment and is worthy of further studies."

基金机构：Chongqing Municipal Health Commission [CSTC2010BB5383]

基金资助正文：This research did receive specific grants from Chongqing Municipal Health Commission (grant number: CSTC2010BB5383).