LncRNA TUBA4B functions as a competitive endogenous RNA to inhibit gastric cancer progression by elevating PTEN via sponging miR-214 and miR-216a/b

[摘要] BackgroundEmerging evidence demonstrates that long non-coding RNA (lncRNA) is an important regulator in tumorigenesis and development. Tubulin Alpha 4B (TUBA4B), a novel lncRNA, was recently proposed as a tumor suppressor in several human cancers. However, its role in gastric cancer (GC) remains unclear. In this study, we aimed to investigate the expression level, clinical implication, biological function and potential regulatory mechanism of TUBA4B in GC.MethodsqRT-PCR was employed to detect the expression of TUBA4B in GC tissues, cell lines and plasma. In vitro and in vivo experiments were carried out using colony formation/CCK-8/transwell invasion/cell apoptosis assay and xenograft tumor model, respectively. mRNA sequencing was used to identify the TUBA4B-related downstream genes.ResultsTUBA4B was significantly decreased in GC tissues, cells and plasma. Low TUBA4B was positively correlated with larger tumor size, lymph node metastasis and advanced TNM stage. Moreover, TUBA4B was identified as an effective biomarker for the diagnosis and prognosis of patients with GC. Functionally, ectopic expression of TUBA4B inhibited GC cell proliferation, invasion and induced apoptosis in vitro as well as dampened tumor growth and metastasis in vivo. Furthermore, TUBA4B was found to be a competitive endogenous RNA (ceRNA) that could physically bind to and sequester miR-214 and miR-216a/b to increase the expression of their common downstream target PTEN, resulting in inactivation of PI3K/AKT signaling pathway, thereby retarding GC progression.ConclusionOur data highlight the compelling regulatory role of TUBA4B in GC, and reactivation of TUBA4B may be a promising therapeutic avenue for GC patients.

[发布日期] 2019-06-03

[关键词] Long non-coding RNA;TUBA4B;Gastric cancer;ceRNA;PI3K/AKT signaling;Biomarker