LncRNA SND1-IT1 facilitates TGF-β1-induced epithelial-to-mesenchymal transition via miR-124/COL4A1 axis in gastric cancer

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.

COL4A1 promotes the proliferation and migration of oral squamous cell carcinoma cells by binding to NID1

“…Conversely, collagens bind to integrins, discoidin domain receptors and tyrosine kinase receptors to influence the behavior of tumor cells ( 27 ). COL4A1, which belongs to the collagen family, serves a tumor-promoting role in several types of cancer ( 28 , 29 ). Wang et al ( 30 ) showed that COL4A1 exerts a promoting effect on proliferation and metastasis in hepatocellular carcinoma via the activation of a FAK-Src signaling pathway.…”

FERMT2 upregulation in CAFs enhances EMT of OSCC and M2 macrophage polarization

“…In addition, it induces M2 polarization of macrophages and facilitates the proliferation, migration, and angiogenesis of cholangiocarcinoma (Deng et al, 2022). COL4A1 and IGFBP4 can also promote EMT of multiple types of cancer and enhance their migration and invasion (Hu et al, 2022; Praveen Kumar et al, 2014; Zhang et al, 2021). In this study, we found that OCAFs with FERMT2 knockdown had significantly weakened EMT‐inducing effects.…”

Identification of Differentially Expressed Intronic Transcripts in Osteosarcoma

“…Interestingly, SND1-IT1 accelerates cell proliferation, migration, and invasion in retinoblastoma [ 21 ]. The transcript also plays a role in epithelial-mesenchymal transition in gastric cancer [ 22 ]. Our results showed that SND1-IT1 interacts with ATXN2L, DSTN, SUGT1, SEPT3, and BDH1 genes.…”