Background: Plasma membrane provides a highly dynamic barriers for cancer cells to interact with their surrounding microenvironment. Membrane tension, a pivotal physical property of plasma membrane, has attracted more and more attention since it plays a role in the progression of various cancers. However, membrane tension related genes (MTRGs) involved in the regulation of colon cancer are not thoroughly understood. This study aimed to identify a prognostic MTRG signature in colon cancer and explore its implications for the disease.Methods: Bulk and Single-cell RNA-seq data and relevant clinical information were obtained from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) database. 44 membrane tension related genes (MTRGs) were obtained through literature. Analysis of differential expressed MTRGs was performed on the RNA-Seq data. By implementing a univariate Cox regression and a LASSO-Cox regression, we developed a prognostic model based on 4 MTRGs. We evaluated the prognostic efficacy of this model using Kaplan–Meier survival curve analysis and receiver operating characteristic (ROC) curve analysis. Moreover, the relationships between this signature and immune cell infiltration, immune status, somatic mutation, pseudo cell differentiation and drug sensitivity were further explored.Results: A 4-MTRG signature was constructed. Risk score derived from the model was further validated as an independent variable for survival prediction. Two risk groups were classified based on the risk score calculated by the 4-MTRG signature. Additionally, we observed a significant difference in immune cells infiltration, such as subsets of CD4 T cells and macrophages, between the high- and low groups. Moreover, in the pseudo-time analysis, TIMP1 was found to express higher as time goes on. Finally, three small molecule drugs, elesclomol, shikonin and bryostatin-1, exhibited binding potential to TIMP-1.Conclusion: The proposed 4-MTRG signature is a promising biomarker to predict clinical outcomes and therapeutic responses in colon cancer patients.

Hepatic fibrosis is the final pathway of chronic liver disease characterized by excessive accumulation of extracellular matrix (ECM), which eventually develop into cirrhosis and liver cancer. Emerging studies demonstrated that Saikosaponin-d (SSd) exhibits a protective role in liver fibrosis. The current study mainly explored the mechanism underlying anti-liver fibrosis of SSd in vivo and in vitro. Transforming growth factor (TGF)-β and carbon tetrachloride (CCl4) were used for creating liver fibrosis model in vitro and in vivo, respectively. The role of SSd in regulating liver fibrosis was assessed through Sirius red and Masson staining, and IHC assay. We found that SSd attenuated remarkably CCl4-induced liver fibrosis as evidenced by decreased collagen level, and decreased expression of fibrotic markers Col 1 and α-SMA. Meanwhile, SSd repressed autophagy activation as suggested by decreased BECN1 expression and increased p62 expression. Compared with HSCs from CCl4-treated group, the primary HSCs from SSd-treated mice exhibited a marked inactivation of autophagy. Mechanistically, SSd treatment enhanced the expression of GPER1 in primary HSCs and in TGF-β-treated LX-2 cells. GPER1 agonist G1 repressed autophagy activation, whereas GPER1 antagonist G15 activated autophagy and G15 also damaged the function of SSd on suppressing autophagy, leading to subsequent increased levels of fibrotic marker level in LX-2 cells. Collectively, our findings highlight that SSd alleviates hepatic fibrosis by regulating GPER1/autophagy pathway.