Fbln5, a member of the short fibulins in the fibulin family of extracellular matrix/matricellular proteins, is involved in interactions with components of the basement membrane and extracellular matrix proteins. It plays key roles in endothelial tissues in many vascular diseases and is also potentially involved in immune-related biological processes [5,7].

Abnormal Fbln5 expression levels are related to various diseases. In gastric cancer, high Fbln5 mRNA levels are associated with a poor prognosis and are significantly correlated with INFc and N3 lymph node metastasis, making it a valuable prognostic indicator [1]. Loss of NDUFS1 promotes gastric cancer progression by activating the mitochondrial ROS-HIF1α-Fbln5 signaling pathway [4]. In high-grade serous ovarian carcinoma, decreased Fbln5 expression is associated with unfavorable prognosis, and Fbln5 overexpression inhibits ovarian cancer cell migration, invasion and proliferation in vitro [6]. In renal clear cell carcinoma, Fbln5 expression is reduced in tumor tissue, and high expression in children and young adults is associated with a favorable prognosis [5]. Fbln5-related cutis laxa is a rare autosomal recessive syndrome [2]. Also, Fbln5 mutations are related to demyelinating Charcot-Marie-Tooth neuropathy, which has a recognizable clinical phenotype [3].

In conclusion, Fbln5 is crucial for maintaining extracellular matrix-related functions and is involved in multiple disease processes. Studies on Fbln5 contribute to understanding the mechanisms of various diseases, including cancers, connective tissue disorders, and neuropathies, providing potential targets for diagnosis and treatment.

References:

1. Bian, Xiulan, Yin, Shengjie, Yin, Xin, Ye, Fei, Zhang, Lei. 2023. Clinical and Biological Significances of FBLN5 in Gastric Cancer. In Cancers, 15, . doi:10.3390/cancers15020553. https://pubmed.ncbi.nlm.nih.gov/36672502/

2. Tekmenuray-Unal, Aysel, Durmaz, Ceren Damla. 2022. FBLN5-Related Cutis Laxa Syndrome: A Case with a Novel Variant and Review of the Literature. In Molecular syndromology, 14, 80-87. doi:10.1159/000525215. https://pubmed.ncbi.nlm.nih.gov/36777703/

3. Safka Brozkova, D, Stojkovic, T, Haberlová, J, Seeman, P, Auer-Grumbach, M. 2020. Demyelinating Charcot-Marie-Tooth neuropathy associated with FBLN5 mutations. In European journal of neurology, 27, 2568-2574. doi:10.1111/ene.14463. https://pubmed.ncbi.nlm.nih.gov/32757322/

4. Chen, Tao, Li, Dongbao, Wang, Yunliang, Qian, Fuliang, Zhou, Jin. 2023. Loss of NDUFS1 promotes gastric cancer progression by activating the mitochondrial ROS-HIF1α-FBLN5 signaling pathway. In British journal of cancer, 129, 1261-1273. doi:10.1038/s41416-023-02409-5. https://pubmed.ncbi.nlm.nih.gov/37644092/

5. Zhang, Ming, Chen, Feng, Feng, Shaoguang, Zhu, Dongsheng, Zhu, Zhitao. 2024. FBLN5 as One Presumably Prognostic Gene Potentially Modulating Tumor Immune Microenvironment for Renal Clear Cell Carcinoma in Children and Young Adults. In Pharmacogenomics and personalized medicine, 17, 27-40. doi:10.2147/PGPM.S442803. https://pubmed.ncbi.nlm.nih.gov/38264064/

6. Li, Rongrong, Wu, Huan, Jiang, Huiyang, Yang, Ning, Kong, Beihua. 2020. FBLN5 is targeted by microRNA‑27a‑3p and suppresses tumorigenesis and progression in high‑grade serous ovarian carcinoma. In Oncology reports, 44, 2143-2151. doi:10.3892/or.2020.7749. https://pubmed.ncbi.nlm.nih.gov/32901854/

7. Zheng, Lin, Yue, Xinyang, Li, Minhui, Chen, Ruihan, Dong, Honglin. 2022. Contribution of FBLN5 to Unstable Plaques in Carotid Atherosclerosis via mir128 and mir532-3p Based on Bioinformatics Prediction and Validation. In Frontiers in genetics, 13, 821650. doi:10.3389/fgene.2022.821650. https://pubmed.ncbi.nlm.nih.gov/35356421/