Bbs9, also known as PTHB1, is a gene encoding a structural component of the ciliary BBSome complex. The BBSome is implicated in trafficking proteins to cilia, which are important for various cellular signaling pathways and biological functions. Mutations in Bbs9 have been associated with Bardet-Biedl syndrome (BBS), a genetically heterogeneous disorder with features like polydactyly, obesity, and retinal dystrophy [3,4].

In a zebrafish model, knockdown of bbs9 led to developmental abnormalities in the retina and brain, including hydrocephaly, and caused a reduced number and length of cilia in Kupffer's vesicle. In mouse IMCD3 cells, Bbs9 knockdown resulted in the absence of cilia, suggesting a conserved key role of Bbs9 in cilia biogenesis and/or function [6]. In lung adenocarcinoma (LUAD), circ-BBS9 (a circular RNA derived from the Bbs9 gene) was significantly downregulated. Overexpression of circ-BBS9 inhibited LUAD cell proliferation, promoted ferroptosis in vitro, and suppressed tumor growth in vivo [1]. In chronic obstructive pulmonary disease (COPD), the level of circ-BBS9 increased in cigarette smoke extract-treated cells, and its silencing decreased apoptotic cell ratio [2]. In testis, a testis-enriched circular RNA circ-Bbs9 was found to play a critical role in Leydig cell proliferation by regulating the levels of cell-cycle related Ccnd2 [5].

In conclusion, Bbs9 is crucial for cilia-related functions. Studies using knockdown models in zebrafish and mouse cells have revealed its role in cilia formation. The circular RNAs derived from Bbs9 also play important roles in diseases such as LUAD, COPD, and in male reproductive system function. These findings help to understand the biological functions of Bbs9 and its potential as a therapeutic target in related diseases.

References:

1. Peng, Daijun, Liang, Mingyu, Li, Lingyu, Chen, Lingling, Guan, Bing. 2024. Circ_BBS9 as an early diagnostic biomarker for lung adenocarcinoma: direct interaction with IFIT3 in the modulation of tumor immune microenvironment. In Frontiers in immunology, 15, 1344954. doi:10.3389/fimmu.2024.1344954. https://pubmed.ncbi.nlm.nih.gov/39139574/

2. Guo, Pujian, Lu, Jing, Lei, Yu. 2023. Significant role of circRNA BBS9 in chronic obstructive pulmonary disease via miRNA-103a-3p/BCL2L13. In BMC pulmonary medicine, 23, 257. doi:10.1186/s12890-023-02540-2. https://pubmed.ncbi.nlm.nih.gov/37442983/

3. Zhang, Yue, Xu, Manhong, Zhang, Minglian, Yang, Guoxing, Li, Xiaorong. 2021. A Novel BBS9 Mutation Identified via Whole-Exome Sequencing in a Chinese Family with Bardet-Biedl Syndrome. In BioMed research international, 2021, 4514967. doi:10.1155/2021/4514967. https://pubmed.ncbi.nlm.nih.gov/34692830/

4. Tang, Hai-Yan, Xie, Fen, Dai, Ru-Chun, Shi, Xiao-Liu. 2021. Novel homozygous protein-truncating mutation of BBS9 identified in a Chinese consanguineous family with Bardet-Biedl syndrome. In Molecular genetics & genomic medicine, 9, e1731. doi:10.1002/mgg3.1731. https://pubmed.ncbi.nlm.nih.gov/34212515/

5. Jia, Minzhi, Li, Xiaoliang, Jiang, Chuan, Qin, Lang, Xu, Wenming. . Testis-enriched circular RNA circ-Bbs9 plays an important role in Leydig cell proliferation by regulating a CyclinD2-dependent pathway. In Reproduction, fertility, and development, 32, 355-362. doi:10.1071/RD18474. https://pubmed.ncbi.nlm.nih.gov/31708014/

6. Veleri, Shobi, Bishop, Kevin, Dalle Nogare, Damian E, Liu, Paul, Swaroop, Anand. 2012. Knockdown of Bardet-Biedl syndrome gene BBS9/PTHB1 leads to cilia defects. In PloS one, 7, e34389. doi:10.1371/journal.pone.0034389. https://pubmed.ncbi.nlm.nih.gov/22479622/