miRNA-223 inhibits epithelial-mesenchymal transition in gastric carcinoma cells via Sp1

Abstract

Abstract. Sp1 plays critical roles in epithelial-mesenchymal transition (EMT) of certain cancer. However, few studies have indicated whether Sp1 is involved in the EMT of gastric cancer, and whether abnormal expression of Sp1 in gastric cancer EMT is regulated in a post-transcriptional manner, and the involvement of miRNAs in this regulation. In this study, we selected 20 cases of gastric cancers, their liver metastases and para-carcinoma tissues to examine the levels of Sp1 protein and mRNA by immunohistochemistry and fluorescent PCR, which showed that Sp1 was increased in gastric cancers and their metastases compared with adjacent tissues, but there was no difference in Sp1 mRNA between these three groups, suggesting changes in Sp1 may be attributed to inactivation of post-transcriptional regulation. We verified by a luciferase reporter system that miRNA-223 binds to 3'-UTR of Sp1 gene and inhibits its translation, in agreement with negative correlation between miRNA-223 and Sp1 protein levels in gastric cancer cells. By employing TGF-β1 to induce MGC-803, BGC-823 and SGC-7901, we successfully built cellular EMT model. Then, we overexpressed miRNA-223 in the model by using a lentiviral system, which diminished EMT indicators and suppressed proliferation and invasion ability, and induced apoptosis. Finally, we verified the specificity of the regulation pathway miRNA-223/Sp1/EMT. These findings suggest that low expression of miRNA-223 in gastric cancer cells is an important cause for EMT. miRNA-223 specifically regulates the EMT process of gastric cancer cells through its target gene Sp1. Overexpression of miRNA-223 in these cells inhibits EMT via the miRNA-223/Sp1/EMT pathway.

7,12‐Dimethylbenz[α]anthracene increases cell proliferation and invasion through induction of Wnt/β‐catenin signaling and EMT process

“…The transcription factor specificity protein 1 (Sp1) is widely involved in cancer cell proliferation, migration, and invasion . Recently, it was reported that Sp1 might be related to the activation of Wnt/β‐catenin signaling and the induction of the EMT process through genetic regulation . To identify whether DMBA induced cell proliferation and migration through Sp1 regulation, we investigated the influence of DMBA on Sp1 expression.…”

“…reported that Sp1 might be related to the activation of Wnt/b-catenin signaling and the induction of the EMT process through genetic regulation [49][50][51]. To identify whether DMBA induced cell proliferation and migration through Sp1 regulation, we investigated the influence of DMBA on Sp1 expression.…”

miR-192-5p suppresses the progression of lung cancer bone metastasis by targeting TRIM44

“…Accumulating evidence has demonstrated that miRNAs are involved in cell proliferation, migration, and invasion in malignancy, such as lung cancer bone metastasis 11,13,14,17,19 . For instance, HE et al 29 revealed that downregulation of miR-20b may dramatically suppress H22 cell proliferation by directly targeting PTEN.…”

“…Recent studies have revealed that miRNAs are implicated in various cellular processes [13][14][15] . In addition, many studies have already demonstrated that miRNA dysfunction is involved in the occurrence and progression of malignancies, such as breast cancer, gastric carcinoma, prostate cancer, and lung cancer [16][17][18][19] . In recent years, various studies have shown that miR-192-5p is significantly downregulated in malignant carcinoma, while miR-192-5p overexpression may play a potential role in suppressing tumourigenesis through different mechanisms 20,21 .…”

MIR-107, MIR-223-3P and MIR-21-5P Reveals Potential Biomarkers in Penile Cancer

“…In PC, the first large-scale study with microRNAs analysis was conducted by Zhang et al, (2015), and some differentially expressed microRNAs were identified, such as miR-107, and miR-223-3p. These micro RNAs were described related with metastasis, invasion, transport, and colonization in cancer (Gao et al, 2016;Hu et al, 2016;Markou et al, 2016;Mavrakis et al, 2011). Since PC is often accompanied with lymph node metastases, the involvement of these miRNAs in prognosis of this disease was checked.…”