期刊
JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY
卷 36, 期 7, 页码 1877-1888出版社
WILEY
DOI: 10.1111/jgh.15362
关键词
BRCC3; GC; miR‐ 126‐ 5p; PI3K; Akt; mTOR pathway; TMPO‐ AS1
The study found that TMPO-AS1 is highly expressed in gastric cancer tissues and cells, promoting proliferation, migration, and angiogenesis of gastric cancer cells, and upregulating BRCC3 expression by acting as a competing endogenous RNA for miR-126-5p. The TMPO-AS1/miR-126-5p/BRCC3 axis contributes to gastric cancer progression by regulating the PI3K/Akt/mTOR pathway.
Background and Aim Gastric cancer (GC) is an aggressive tumor featured by uncontrolled cell proliferation and metastasis. In recent years, long noncoding RNAs (lncRNAs) act as crucial regulators and biological markers in multiple cancers. LncRNA TMPO-AS1 has been revealed to be an oncogene in some cancers. Nevertheless, there is little known about the biological role of TMPO-AS1 in GC. Methods Reverse transcription-quantitative polymerase chain reaction analysis was used to examine the expression level of TMPO-AS1 in GC tissues and cells. Cell Counting Kit-8, colony formation, wound healing assays, and western blot analysis were performed to determine the role of TMPO-AS1 in GC cells. RNA pull-down, luciferase reporter, and RNA immunoprecipitation assays were used to test the interaction among TMPO-AS1, miR-126-5p, and BRCC3. Results TMPO-AS1 was highly expressed in GC tissues and cells. Upregulated TMPO-AS1 was closely associated with adverse prognosis of GC patients. Functional assays showed that TMPO-AS1 promoted GC cell proliferation, migration, and angiogenesis. Furthermore, it was found that TMPO-AS1 acted as a competing endogenous RNA for miR-126-5p to upregulate BRCC3 expression. Rescue assays revealed that TMPO-AS1 facilitated cellular progression of GC by sponging miR-126-5p and upregulating BRCC3. In addition, we found that the effects of the TMPO-AS1/miR-126-5p/BRCC3 axis on GC cell progression were related to the PI3K/Akt/mTOR pathway. Conclusions Our study demonstrated that the TMPO-AS1/miR-126-5p/BRCC3 axis was involved in GC progression via the regulation of PI3K/Akt/mTOR pathway, which might provide a potential therapeutic strategy for GC.
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