Abstract
Gastric adenocarcinoma, which originates from the gastric mucosal epithelium, has the highest incidence among various malignant tumours in China. As a crucial long non-coding RNA, metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been suggested to play an important role in many tumours. Here, we aimed to investigate the role and underlying mechanism of MALAT1 in gastric adenocarcinoma. Quantitative reverse transcription polymerase chain reaction was applied to determine the expression levels of MALAT1 in serum and cell lines. A CCK-8 assay and a clonogenic survival assay were used to examine cell proliferation and apoptosis. The protein level of RAC-γ serine/threonine-specific protein kinase (AKT3) was determined by western blot. Our results showed that MALAT1 was highly expressed in the serum of patients with gastric adenocarcinoma and in cell lines. Downregulating MALAT1 inhibited proliferation and promoted apoptosis of MGC-803 cells. In addition, MALAT1 directly targeted and decreased the expression of miR-181a-5p, which in turn upregulated the expression of AKT3. Further, overexpressing miR-181a-5p or directly inhibiting the AKT pathway with the inhibitor ipatasertib exhibited similar effects to MALAT1 knockdown. Our research proposes a novel mechanism where the role of MALAT1 is dependent on the MALAT1/miR-181a-5p/AKT3 axis. MALAT1 competes with AKT3 for miR-181a-5p binding, thereby upregulating the AKT3 protein level and ultimately promoting the growth of gastric adenocarcinoma.
Highlights
Gastric cancer is a common malignant tumour of the digestive tract, and has a high incidence and mortality in China [1]
In order to identify the function of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in gastric adenocarcinoma, we first examined the serum levels of MALAT1 in 70 patients with gastric adenocarcinoma and 70 healthy controls by quantitative reverse transcription polymerase chain reaction
We conclude that MALAT1 is highly expressed in patients with gastric adenocarcinoma and correlates with higher malignancy
Summary
Gastric cancer is a common malignant tumour of the digestive tract, and has a high incidence and mortality in China [1]. Gastric adenocarcinoma is a type of gastric cancer caused by malignant transformation of gastric gland cells [2]. The incidence of gastric adenocarcinoma accounts for 95% of gastric malignancies [3]. According to the Lauren classification, gastric adenocarcinoma is generally divided into two types, intestinal and diffuse. Gastric adenocarcinoma tends to invade the stomach wall, penetrate the muscular mucosa and submucosa and destroy the muscularis propria [4]. The aetiology and pathogenesis of gastric adenocarcinoma are still unclear, limiting the efficacy of clinical treatment for patients with gastric adenocarcinoma
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