Yongpan Xu1, Ming Dong2, Jiehong Wang1, Weihan Zhao1, Min Jiao3. 1. Department of Gastroenterology, Affiliated Hospital of Shaanxi University of Chinese Medicine, Xianyang, 712000, Shaanxi, China. 2. Department of Surgical Oncology, Affiliated Hospital of Shaanxi University of Chinese Medicine, Xianyang, 712000, Shaanxi, China. 3. Department of Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, No. 277 West Yanta Road, Xi'an, 710061, Shaanxi, China. jiaomin3650000@163.com.
Abstract
BACKGROUND: Gastric cancer (GC) is a prevalent type of digestion system malignancies. Dysregulation of long non-coding RNAs (lncRNAs) has been proven to be prognostic factors and biological regulators in human cancers. AIMS: The current study aimed to explore the role of long intergenic non-protein coding RNA 1436 (LINC01436) and its underlying mechanism in the progression of GC. METHODS: RT-qPCR was conducted to measure RNA expression. Western blot was used for exploration of protein level. CCK-8, caspase-3 activity, and transwell assays were applied to evaluate the proliferative, apoptotic, and migratory abilities of GC cells, respectively. Mechanical experiments were used to probe the molecular interplay between genes. RESULTS: High LINC01436 level suggested low overall survival in GC patients, and LINC01436 was highly expressed in GC tissues and cells. Besides, LINC01436 knockdown hampered cell proliferation and migration, while facilitated cell apoptosis. Mechanistically, LINC01436 upregulated mitogen-activated protein kinase 1 (MAPK1) expression by competitively binding with miR-585-3p and inhibiting miR-585-3p expression. Furthermore, LINC01436 negatively regulated miR-585-3p expression by enhancing the zeste 2 polycomb repressive complex 2 subunit (EZH2)-induced trimethylation of histone H3 at lysine 27 (H3K27me3) on miR-585-3p promoter. Final rescue assays revealed that overexpression of MAPK1 could rescue the suppressive influence of LINC01436 depletion on GC progression. CONCLUSIONS: LINC01436 epigenetically silences miR-585-3p and acts as miR-585-3p to upregulate MAPK1 expression and promote GC progression.
BACKGROUND: Gastric cancer (GC) is a prevalent type of digestion system malignancies. Dysregulation of long non-coding RNAs (lncRNAs) has been proven to be prognostic factors and biological regulators in human cancers. AIMS: The current study aimed to explore the role of long intergenic non-protein coding RNA 1436 (LINC01436) and its underlying mechanism in the progression of GC. METHODS: RT-qPCR was conducted to measure RNA expression. Western blot was used for exploration of protein level. CCK-8, caspase-3 activity, and transwell assays were applied to evaluate the proliferative, apoptotic, and migratory abilities of GC cells, respectively. Mechanical experiments were used to probe the molecular interplay between genes. RESULTS: High LINC01436 level suggested low overall survival in GC patients, and LINC01436 was highly expressed in GC tissues and cells. Besides, LINC01436 knockdown hampered cell proliferation and migration, while facilitated cell apoptosis. Mechanistically, LINC01436 upregulated mitogen-activated protein kinase 1 (MAPK1) expression by competitively binding with miR-585-3p and inhibiting miR-585-3p expression. Furthermore, LINC01436 negatively regulated miR-585-3p expression by enhancing the zeste 2 polycomb repressive complex 2 subunit (EZH2)-induced trimethylation of histone H3 at lysine 27 (H3K27me3) on miR-585-3p promoter. Final rescue assays revealed that overexpression of MAPK1 could rescue the suppressive influence of LINC01436 depletion on GC progression. CONCLUSIONS: LINC01436 epigenetically silences miR-585-3p and acts as miR-585-3p to upregulate MAPK1 expression and promote GC progression.