Long non-coding RNA LINC00707, a prognostic marker, regulates cell proliferation, apoptosis, and EMT in esophageal squamous cell carcinoma.

ABSTRACT

BACKGROUND: Long intergenic non-protein coding RNA 707 (LINC00707) has been identified as a cancer-associated long non-coding RNA (lncRNA) in a variety of cancers. However, the functions and molecular mechanisms of LINC00707 in esophageal squamous cell carcinoma (ESCC) are still unclear. METHODS: The expression of LINC00707 in esophageal cancer (ESCA) and ESCC tissues was determined by online tools, RNA-sequence (RNA-seq) dataset, and quantitative real time polymerase chain reaction (qRT-PCR). The associations between LINC00707 expression and clinicopathologic features and prognosis were investigated. Furthermore, the expression of LINC00707 in ESCC cell lines was determined by qRT-PCR. Then, using LncACTdb 2.0 database, combined with loss-of-function assay verification, we investigated the biologic role of LINC00707 in ESCC cell growth, apoptosis, invasion, and migration by CCK-8, colony formation, flow cytometry and transwell assays. Finally, western blot was used to evaluate the regulatory effect of LINC00707 on PI3K/Akt signaling pathway. RESULTS: Increased LINC00707 expression was exhibited in ESCC tissues and cell lines. High expression of LINC00707 was positively associated with higher tumor-node-metastasis (TNM) stage and lymph node metastasis. Furthermore, LINC00707 expression was significantly higher in patients who drink alcohol, have lymph node metastasis, and harbor higher tumor stage. In addition, Kaplan-Meier survival analysis and receiver operating characteristic (ROC) curve confirmed the feasibility of LINC00707 as a prognostic signature or diagnostic marker. Functional experiments showed that LINC00707 downregulation suppressed ESCC cell proliferation, and metastasis, and induced ESCC cell apoptosis. Mechanistic investigation demonstrated that LINC00707 activated the PI3K/Akt signaling pathway in ESCC cells. CONCLUSIONS: Our findings suggest LINC00707 functions as an oncogenic lncRNA in ESCC, and imply that LINC00707 may be a promising prognostic biomarker and therapeutic target for ESCC patients.