Long non-coding RNA LINC00152 plays an oncogenic role via targeting STAT3 and c-MYC signaling in esophageal adenocarcinoma

Abstract

ObjectiveEsophageal cancer remains a threat to public health with an increasing incidence and low survival rate worldwide. In the past thirty years the rates for esophageal adenocarcinoma (EAC) have increased over 500%. Prior studies have linked Barrets esophagus (BE), Low grade dysplasia (LGD), and High grade dysplasia (HGD) as general precursors to EAC. However, the exact pathways by which EAC occurs have not been uncovered. Recent genomic studies have discovered a new family of active RNA species named long non-coding RNAs (lncRNAs). Of which, LINC00152 has been linked to several human cancers and shown to promote cell proliferation in lung, gastric, hepatocellular, colorectal, and clear cell renal carcinoma. This study is to investigate the roles of LINC00152 in EAC using EAC patient data and EAC cell lines. MethodsWe used LINC00152 specific siRNAs to knockdown LINC00152 and used the Gateway cloning method to generate stable overexpression of LINC00152 in Flo, OE19, and OE33 cell lines for in vitro study. The cells were tested for changes in cell proliferation, colony formation, invasion and migration. Real-time PCR assay was used for detecting mRNA expression and Western blot was used for examining altered protein expressions affected by LINC00152. Data analysis were performed using excel and Prism. Statistical differences were assessed using the Students T-test. Survival analysis was done using Kaplan-Meier estimates. ResultsThis study found that high levels of LINC00152 correlated positively with tumor progression, invasive potential, and TNM stage advancement in EAC. LINC00152 knockdown could inhibit cell proliferation, colony formation, and cell invasion. Western blot and Real-time PCR results suggests that LINC00152 may active via STAT3 and c-MYC signaling as both demonstrated changes following knockdown and overexpression experiments. ConclusionsThis study indicated that LINC00152 might be used as both a biomarker and a novel therapeutic target to improve the outcome for EAC patients. Further characterization of LINC00152 as a novel therapeutic target for EAC is warranted.