Downregulation of long non-coding RNA LINP1 inhibits the malignant progression of esophageal squamous cell carcinoma.

Background: Long noncoding RNA (lncRNA) in non-homologous end joining pathway 1 (LINP1) contributes to tumorigenesis in various cancers. However, little has been known about the role of LINP1 in esophageal squamous cell carcinoma (ESCC). Methods: LINP1 was selected as the target lncRNA by bioinformatics analysis. The relationship between LINP1 expression and prognosis was analyzed in 122 ESCC patients. LINP1 status was evaluated by fluorescence in situ hybridization (FISH) and quantitative real-time PCR (qRT-PCR) in normal esophageal tissues, ESCC tissues and EC9706 cells. Short hairpin RNA transfection was used to silence LINP1 in EC9706 cells. Clone formation assay, transwell migration assay, flow cytometry, and tumorigenesis experiment were performed to evaluate the malignant phenotype of EC9706 cells. Results: Bioinformatics analysis showed that LINP1 was the most significantly differentially expressed lncRNA. Upregulation of LINP1 was observed in ESCC tissues and EC9706 cells. High LINP1 expression had close correlation with larger tumor size (P=0.009), tumor invasion (P=0.015), lymph nodes metastasis (P=0.044), and advanced TNM stage (P=0.010). LINP1 overexpression was an independent prognostic factor of ESCC patients (P=0.034). LINP1 knockdown decreased the proliferative and migratory abilities of EC9706 cells, and promoted apoptosis and cell cycle arrest at the G2/GM phase. Epithelial-mesenchymal transition (EMT) related proteins such as N-cadherin, vimentin, snail and slug were downregulated while E-cadherin was up-regulated significantly in shRNA-LINP1 cells. In the xenograft model, knockdown of LINP1 suppressed ESCC tumorigenesis in vivo. Conclusions: LINP1 was prognostic indicator of ESCC and silencing of LINP1 could inhibit the malignant behavior of ESCC cells.