J Cancer 2022; 13(10):3013-3021. doi:10.7150/jca.73112 This issue

Research Paper

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

Rongxian Cao1,2, Zhiqiang Zhang2, Chen Tian1, WeiWei Sheng1, Qi Dong2, Ming Dong1✉

1. Department of Gastrointestinal Surgery, The First Hospital of China Medical University, China.
2. Department of General Surgery, The People's Hospital of Liaoning Province, Shenyang, China.

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Citation:
Cao R, Zhang Z, Tian C, Sheng W, Dong Q, Dong M. Down-regulation of MSMO1 promotes the development and progression of pancreatic cancer. J Cancer 2022; 13(10):3013-3021. doi:10.7150/jca.73112. Available from https://www.jcancer.org/v13p3013.htm

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Abstract

Graphic 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.

Keywords: MSMO1, Pancreatic Cancer, EMT, PI3K-AKT-mTOR, Progression