Abstract
The transformation of tumor cells from an epithelial to a mesenchymal-like phenotype, designated as epithelial-to-mesenchymal transition (EMT), represents a key hallmark of human cancer metastasis, including gastric cancer (GC). However, a large set of non-coding RNAs have been studied for their functions that initiate or inhibit this phenotypic switch in GC cells by regulating oncogenes or tumor suppressors. In this paper, we aimed to identify lncRNA SND1-IT1, miR-124, and COL4A1 gene in the context of GC with a specific focus on their effects on transforming growth factor β1 (TGF-β1)-induced EMT. The study included 52 paired samples of lesion tissues and adjacent lesion-free tissues surgically resected from patients diagnosed with GC. HGC-27 cells were stimulated with exogenous TGF-β1 (2 ng/mL). Expression of lncRNA SND1-IT1, miR-124, and COL4A1 was determined by RT-qPCR. CCK-8 assays, Transwell assays, immunoblotting analysis of EMT-specific markers, and tumor invasion markers were performed to evaluate cell viability, migration, and invasion of cultured HGC-27 cells. Luciferase activity assay was employed to examine miR-124 binding with lncRNA SND1-IT1 and COL4A1, respectively. LncRNA SND1-IT1 was upregulated in GC tissues and cells. TGF-β1-stimulated EMT and regulated lncRNA SND1-IT1, miR-124, and COL4A1 expressions in HGC-27 cells. LncRNA SND1-IT1 knockdown tempered HGC-27 cell viability, migration and invasion. LncRNA SND1-IT1 participated in TGF-β1-stimulated EMT in GC by sponging miR-124. MiR-124 attenuated TGF-β1-stimulated EMT in GC by targeting COL4A1. These results primarily demonstrated TGF-β1 can regulate cancer cell migration, invasion and stimulate EMT through the SND1-IT1/miR-124/COL4A1 axis in GC.
Highlights
Gastric cancer (GC) is one of the most lethal malignancies and contributes to a substantial health care burden to patients
LncRNA SND1-IT1 was upregulated in GC tissues and cells Initially, Long non-coding RNAs (lncRNAs) SND1-IT1 was quantified in human cancer tissue samples surgically resected from GC patients by RT-qPCR
We found that lncRNA SND1-IT1 exhibited a higher expression level in four selected GC cells (HGC27, AGS, NCI-N87, and MKN74) than in GES1 cells (Fig. 1B)
Summary
Gastric cancer (GC) is one of the most lethal malignancies and contributes to a substantial health care burden to patients. Laparoscopy-assisted distal gastrectomy (LADG) and open distal gastrectomy (ODG) have been suggested as standard treatment options for GC at an early stage [8]. Due to the lack of marked symptoms in an early stage of GC, many patients present advanced disease at their initial diagnosis [9]. Epithelial–mesenchymal transition (EMT) is a prominent process in tumor development by converting epithelial phenotypic cells into mesenchymal phenotypic cells [10]. Transforming growth factor (TGF)-β1 is a well-characterized contributor to the process of EMT [11]. EMT usually limits total surgical resection and leads to therapeutic resistance, whereas there is limited knowledge about signaling pathways and effector molecules that initiate this phenotypic switch in GC. Molecular processes and the downstream mechanisms involved in TGF-β1-stimulated EMT in GC remain enigmatic and merit further investigation
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