MALAT1 promotes gastric adenocarcinoma through the MALAT1/miR-181a-5p/AKT3 axis

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.