Down-regulation of MSMO1 promotes the development and progression of pancreatic cancer

Abstract

Background: Methylsterol monooxygenase 1 (MSMO1), as a completely unique tumor biomarker, plays a vital role in the malignant progression of various cancer. Until now, the potential function and pathway of MSMO1 in the development of pancreatic cancer (PC) has not been explored yet, to our knowledge. Methods: We systematically explored the detail function of MSMO1 in Epithelial-mesenchymal transition (EMT) and cell proliferation of PC in vitro and in vivo. Results: MSMO1 expression was much lower in PC tissues than that in paired normal pancreas. MSMO1 positive expression was negatively associated with T stage, lymph node metastasis and vascular permeation of PC patients. Meanwhile, positive MSMO1 expression indicated a significantly better prognosis and an independent favorable prognostic factor. MSMO1 silencing promoted cell invasion and migration via activating EMT and PI3K-AKT-mTOR pathway [p-PI3K (Tyr458), p-AKT (Ser473) and p-mTOR (Ser2448)] in Capan-2, Panc-1 and SW1990 cells. In vivo, subcutaneous tumor size was enhanced by MSMO1 silencing following with the consistent change of EMT and PI3K/AKT signaling shown in vitro. The motivation of EMT and PI3K-AKT-mTOR pathway was also demonstrated in MSMO1 silencing mouse PANC02 cells. Conclusion: Down-regulation of MSMO1 in PC was associated with advanced progression and poor prognosis of PC patients. MSMO1 acts as a tumor suppressor via inhibiting the aggressive malignant biology of PC accompanying with regulating EMT and PI3K/AKT signaling.

Identification of iron metabolism-related predictive markers of endometriosis and endometriosis-relevant ovarian cancer

“…[33] Furthermore, MSMO1 is involved in the biosynthesis and metabolism of sterols and cholesterol. [34] Previous studies reported that MSMO1 expression is up-regulated in cervical cancer [35,36] and down-regulated in hepatocellular carcinoma, [37] cholesterol synthesis in chondrocytes, [38] pancreatic cancer, [39] and iron overload, [40] which is consistent with our results. NCOA4 encodes a selective receptor that mediates ferritinophagy and the cytosolic iron storage complex [41,42] and plays a selective regulatory role in the case of iron deficiency or iron overload.…”

MSI2 regulates NLK-mediated EMT and PI3K/AKT/mTOR pathway to promote pancreatic cancer progression

“…Our results demonstrate that NLK can promote the occurrence and development of EMT in pancreatic cancer cells. However, due to different types of cancer and their associated cellular environments, the role of NLK may vary or even be opposite in different types of cancer [33] . Reports suggested that NLK overexpression can inhibit the occurrence of EMT and subsequently inhibit the proliferation and migration of non-small cell lung cancer (NSCLC) by affecting E-cadherin protein expression [34; 35] .…”

Integrative analysis of ex vivo studies and microarray reveals the novel inhibitor effects of trehalose on the pathogenesis of pterygium

“…In our microarray analysis, we determined that downregulation is associated with different biological processes, including protein complexes involved in cell adhesion ( FZD7 ), vasculature development( PTGS2, C3, IL6 ), development of angiogenesis ( SERPINF, C3, ADAMTS1, HMOX1, CXCL8, PTGS2 ), cell migration ( PTGS2, CXCL12, CYGB, BMP2, LRRC15, CXCL8, ENPP2, HAS2, NR4A2), cell differentiation ( BMP2, LIF ), tube development (PTGS2, NR4A1, HSD11B1, ANG, LIF BMP2, ID1, ADAMTS1, HMOX1 ), and cell–matrix adhesion ( SNED1 ). Steroid and lipid metabolism, dysregulated cell proliferation, migratory activity, regulatory molecules in cell adhesion, and extracellular matrix play essential roles in the pathogenesis of pterygium (Cao et al., 2022; Kim et al., 2013; Liu et al., 2013).…”