Abstract

BackgroundAlthough the medical level is constantly improving, cancer is still a major disease that threatens human health, and very effective treatments have not been found. In recent years, studies have found that four-transmembrane superfamily proteins are involved in multiple stages of tumorigenesis and development, but their expression and function in tumors have not been systematically studied.MethodsWe used the Oncomine database to analyze the mRNA expression levels of TSPAN family in various cancers. Then differentially expressed genes were screened out and verified by liver cancer, colorectal cancer, and gastric cancer cells by q-PCR and Western blot analysis. CCK8 and EDU analysis are used to detect cell proliferation, Cell wound scrape assay and Cell invasion assay are used to analyze cell invasion and metastasis. Nude tumor formation test used to verify the tumor suppressive effect of TSPAN7 in vivo.ResultsDifferential analysis of 33 TSPAN proteins revealed that a total of 11 proteins showed differential expression in 10% of independent analyses, namely TSPAN1, TSPAN3, TSPAN5, TSPAN6, TSPAN7, TSPAN8, TSPAN13, TSPAN25, TSPAN26, TSPAN29, TSPAN30. TSPAN7 is the only four-transmembrane protein with reduced expression in three types of digestive tract tumors, so we chose TSPAN7 to be selected for cellular and molecular level verification. We found that compared with normal cells, the expression of TSPAN7 in liver cancer cells was significantly reduced, while the expression of gastric and colon cancer was not significantly different from that of normal cells. In addition, we also found that the high expression of Tspan7 not only inhibited the proliferation of HCC-LM3 cells, but also inhibited its invasion and metastasis.ConclusionsOur study evaluated the expression and function of the TSPANs family in digestive cancers and explored TSPAN7 in hepatoma cells in detail. We found some members of the TSPAN family show significant expression differences between cancer and normal tissues, of which TSPAN7 may be a potential biomarker for liver cancer.

Highlights

  • The medical level is constantly improving, cancer is still a major disease that threatens human health, and very effective treatments have not been found

  • Expression levels of the TSPAN family members in human cancers To investigate whether TSPAN family proteins are differentially expressed between tumor patients and normal populations, we analyzed the expression of 33 members of the four-transmembrane protein family in 21 common tumors through the Oncomine database

  • Differential analysis of 33 TSPAN proteins revealed that a total of 11 proteins showed differential expression in 10% of independent analyses, namely, TSPAN1, TSPAN3, TSPAN5, TSPAN6, TSPAN7, TSPAN8, TSPAN13, TSPAN25, TSPAN26, TSPAN29, and TSPAN30 (Fig. 1)

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Summary

Introduction

The medical level is constantly improving, cancer is still a major disease that threatens human health, and very effective treatments have not been found. Tetraspanins (TSPANs) are a family of proteins with four transmembrane domains that are found in all multicellular eukaryotes [1]. Qi et al Cancer Cell Int (2020) 20:314 of the TSPAN family are as follows: a small extracellular domain (SEL), a large extracellular loop (LEL), and the intracellular N- and C-termini [3]. TSPANs are a group of evolutionarily conserved transmembrane proteins, but there are small variable domains in their LELs, which may be one of the reasons for the functional differences between isotypes [2]. Some members of the four-transmembrane protein family, such as TSPAN [1] and TSPAN13, have been shown to affect tumor metastasis and progression, but there are few studies on these functions [9, 10]. This study will analyze the differences in TSPAN family expression in cancer patients and normal populations through a public database and will evaluate their prognostic value

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