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E2F1-activated NRSN2 promotes esophageal squamous cell carcinoma progression through AKT/mTOR pathway.

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机构： [1]Department of Thoracic Surgery, the Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China [2]Department of CT&MRI, the Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China [3]Laboratory of Pathology, Hebei Cancer Institute, the Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China [4]Hebei Key Laboratory of Vascular Calcification in Kidney Disease, Hebei Clinical Research Center for Chronic Kidney Disease, the Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China

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Neurensin‑2 (NRSN2) has been reported to act as an oncogene in several types of human cancer. However, the molecular mechanism of NRSN2 in esophageal squamous cell carcinoma (ESCC) remains to be elucidated.The mRNA expression levels of NRSN2 in ESCC tissues and cell lines were evaluated by quantitative real-time PCR (qRT-PCR). The protein expression levels of NRSN2 in ESCC tissues were measured by Immunohistochemical (IHC) method. Luciferase reporter and chromatin immunoprecipitation assays were conducted to confirm the upstream transcription factor of NRSN2. Loss- and gain-function assays were conducted to evaluate the effects of NRSN2 on ESCC cells proliferation, migration, and invasion. The function of NRSN2 was validated in vivo using tumor xenografts. The relationship between NRSN2 and AKT/mTOR pathway were confirmed by western blot assay.The expression level of NRSN2 was increased in ESCC tissues and cell lines. High expression level of NRSN2 was correlated with depth of invasion, lymph node metastasis, TNM stage, and poor prognosis of ESCC patients. NRSN2 was transcribed by E2F1. Knockdown of NRSN2 significantly inhibited ESCC cells proliferation, migration, and invasion, whereas NRSN2 overexpression showed reverse phenotypes. Overexpression of NRSN2 also enhanced ESCC tumorigenicity in vivo. Furthermore, the E2F1/NRSN2 axis promoted proliferation, migration, and invasion of ESCC cells by activating the AKT/mTOR pathway.NRSN2 is a direct transcriptional target of E2F1 to promote tumor progression in ESCC. NRSN2 may be a diagnostic biomarker or treatment target for ESCC.Copyright © 2022 The Authors. Published by Elsevier GmbH.. All rights reserved.

基金：

基金编号： No. 81472335 No. 81572441 No. 81772612 to Zhiming Dong] Natural Science Foundation of Hebei Province [No. H2019206664 No. H2020206363 to Wei Guo

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出版当年[2022]版：

大类 | 4 区医学

小类 | 3 区病理学

最新[2025]版：

大类 | 4 区医学

小类 | 3 区病理学

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出版当年[2022]版：

Q2 PATHOLOGY

最新[2024]版：

Q2 PATHOLOGY

影响因子： 3.2 最新[2024版] 2.8 最新五年平均 2.8 出版当年[2022版] 2.7 出版当年五年平均 3.309 出版前一年[2021版] 2.9 出版后一年[2023版]

第一作者：

第一作者机构： [1]Department of Thoracic Surgery, the Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China

通讯作者：

通讯机构： [3]Laboratory of Pathology, Hebei Cancer Institute, the Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China [*1]Hebei Cancer Institute, the Fourth Hospital of Hebei Medical University, Jiankang Rd. 12, Shijiazhuang 050011, Hebei Province, China.

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