Msmo1, also known as SC4MOL, encodes methylsterol monooxygenase 1 which catalyzes C4-methylsterols demethylation in the cholesterol biosynthesis pathway [3,4,5,6]. Cholesterol biosynthesis is crucial for maintaining cell membrane integrity, cell signaling, and various physiological functions. Genetic models can provide insights into how Msmo1 affects these processes.

In pancreatic cancer, down-regulation of Msmo1 promotes cell invasion, migration, and subcutaneous tumor growth in vivo by activating EMT and the PI3K-AKT-mTOR pathway, indicating it acts as a tumor suppressor [2]. In cervical cancer, up-regulation of Msmo1 is associated with poor survival, being an independent risk factor for overall, disease-specific, and progression-free survival [3]. In esophageal cancer, MAGEA6 positively regulates Msmo1, promoting cell invasion and migration [4]. Also, Msmo1 deficiency is an autosomal recessive disorder of distal cholesterol metabolism, causing growth and developmental delay, often with congenital cataracts, microcephaly, psoriasiform dermatitis, and immune dysfunction [1,6]. Oral and topical cholesterol supplements and statins can improve the condition [1,6].

In conclusion, Msmo1 is essential in cholesterol biosynthesis. Its dysregulation is linked to various diseases. Mouse models and patient-based studies have shown its role as a tumor suppressor in pancreatic cancer and a risk factor in cervical cancer. Msmo1 deficiency is associated with a rare neurodevelopmental disorder. Understanding Msmo1 function can offer potential therapeutic strategies for related diseases.

References:

1. Tkemaladze, Tinatin, Bratland, Eirik, Bregvadze, Kakha, Houge, Gunnar, Douzgou, Sofia. 2023. MSMO1 deficiency: a potentially partially treatable, ultrarare neurodevelopmental disorder with psoriasiform dermatitis, alopecia and polydactyly. In Clinical dysmorphology, 32, 97-105. doi:10.1097/MCD.0000000000000461. https://pubmed.ncbi.nlm.nih.gov/37195326/

2. Cao, Rongxian, Zhang, Zhiqiang, Tian, Chen, Dong, Qi, Dong, Ming. 2022. Down-regulation of MSMO1 promotes the development and progression of pancreatic cancer. In Journal of Cancer, 13, 3013-3021. doi:10.7150/jca.73112. https://pubmed.ncbi.nlm.nih.gov/36046654/

3. Zou, Jing, Liu, Sha, Long, Jian. 2024. Up-regulation of MSMO1 was associated with poor survival in cervical cancer. In Translational cancer research, 13, 5316-5327. doi:10.21037/tcr-24-243. https://pubmed.ncbi.nlm.nih.gov/39525016/

4. Liu, Manyu, Li, Jintao, Wang, Yangjunqi, Wang, Minglian, Li, Changshuo. 2022. MAGEA6 positively regulates MSMO1 and promotes the migration and invasion of oesophageal cancer cells. In Experimental and therapeutic medicine, 23, 204. doi:10.3892/etm.2022.11127. https://pubmed.ncbi.nlm.nih.gov/35126707/

5. Zheng, Guangfei, Wang, Zhuan, Fan, Yuchun, Chen, Su, Jiang, Lihe. 2021. The Clinical Significance and Immunization of MSMO1 in Cervical Squamous Cell Carcinoma Based on Bioinformatics Analysis. In Frontiers in genetics, 12, 705851. doi:10.3389/fgene.2021.705851. https://pubmed.ncbi.nlm.nih.gov/34759952/

6. Kalay Yildizhan, Incilay, Gökpınar İli, Ezgi, Onoufriadis, Alexandros, Kutlay, Nüket Yürür, Kundakci, Nihal. 2020. New Homozygous Missense MSMO1 Mutation in Two Siblings with SC4MOL Deficiency Presenting with Psoriasiform Dermatitis. In Cytogenetic and genome research, 160, 523-530. doi:10.1159/000511126. https://pubmed.ncbi.nlm.nih.gov/33161406/