Upregulated long non‑coding RNA LincIN promotes tumor progression via the regulation of nuclear factor 90/microRNA‑7/HOXB13 in esophageal squamous cell carcinoma

Abstract

Long non-coding RNA LincIN has been reported to be overexpressed and to be involved in the metastasis of breast cancer. However, the expression and role of LincIN in esophageal squamous cell carcinoma (EScc) remain unsolved. In the present study, LincIN expression was examined in EScc by RT-qPcR, and the roles of LincIN in EScc were determined using cell growth, migration and invasion assays. In addition, the effects of LincIN on nuclear factor 90 (NF90) and microRNA/miR (miR)-7 were examined by RNA immunoprecipitation assay, RT-qPcR, dual-luciferase reporter assay and western blot analysis. The results revealed that LincIN expression was significantly increased in ESCC tissues and cell lines. The increased expression of LincIN was positively associated with invasion depth, lymph node metastasis, TNM stage and a poor prognosis. Functional assays revealed that the overexpression of LincIN promoted EScc cell growth, migration and invasion. Mechanistic analysis revealed that LincIN physically bound to NF90, enhanced the binding between NF90 and primary miR-7 (pri-miR-7), and further enhanced the inhibitory effects of NF90 on miR-7 biogenesis. Therefore, LincIN downregulated miR-7 expression in EScc. The expression of miR-7 inversely correlated with that of LincIN in EScc tissues. By downregulating miR-7, LincIN increased the expression of HOXB13, a target of miR-7. The overexpression of miR-7 or the depletion of HOXB13 both attenuated the tumor-promoting roles of LincIN in EScc cell growth, migration and invasion. On the whole, the findings of the present study suggest that LincIN is overexpressed and plays an oncogenic role in EScc via the regulation of the NF90/miR-7/HOXB13 axis. Thus, LincIN may prove to be a promising prognostic biomarker and therapeutic target for EScc.

Roles of long non‑coding RNAs in esophageal cell squamous carcinoma (Review)

“…LincIN has been shown to bind to interleukin enhancer binding factor 3 (NF90), enhancing NF90's binding to prim-miR-7 and further inhibiting miR-7. This resulted in increased homeobox B13 expression, promoting the growth, migration and invasion of TE-1 and ECA109 cells, which correlated with invasion, lymph node metastasis, TNM staging and prognosis ( 11 ). LINC02042 enhanced the viability, invasion and growth of KYSE30 and KYSE150 cells.…”

“…It has been established that lncRNAs play a crucial role in the progression of ESCC. Clinically, lncRNAs have been associated with various aspects of ESCC, including lymph node metastasis, tumor size ( 4 ), tumor node metastasis (TNM) stage ( 3 ), prognosis ( 5 ), overall survival (OS) rate ( 6 ), pathological grade of differentiation ( 7 ), survival duration ( 8 ), malignancy grade ( 9 ), distant metastasis ( 10 ), depth of invasion ( 11 ) and postoperative metastasis ( 12 ). In ESCC cell lines, lncRNAs have been implicated in processes such as cell proliferation ( 13 ), migration ( 14 ), invasion ( 15 ), epithelial-to-mesenchymal transition ( 16 ), cell cycle progression ( 17 ), radiosensitivity ( 18 ), glycolysis ( 19 ), chemotherapy resistance, apoptosis ( 20 ), angiogenesis ( 21 ), maintenance of stem cell characteristics ( 22 ), as well as autophagy-related events ( 23 ).…”