Fam114a2, a sperm binding protein, is highly conserved across mammals, fungi, and plants. It has been implicated in potential regulatory roles within biological pathways, with prior studies suggesting its link to miR-762 and P63 in spermatogenesis [1].

In a gene knockout (KO) mouse model study, Fam114a2-/-mice demonstrated normal fertility, normal sperm morphology, and no differences in testicular and epididymis histological features or spermatocyte prophase I progression. Also, normal p63 and miR-762 expression was observed, indicating Fam114a2 is not directly involved in mouse spermatogenesis [1].

In bladder cancer, circular RNA circFAM114A2 was downregulated. Overexpression of circFAM114A2 inhibited UCB cell migration, invasion, and proliferation both in vitro and in vivo by sponging miR-762 to regulate ∆NP63 expression [2].

In cutaneous squamous cell carcinoma, miR-497 was found to be lowly expressed, and it promoted cancer progression by targeting FAM114A2 which was highly expressed in cancer tissues compared to normal tissues [3].

Additionally, a genetic variant rs34767465 associated with primary non-response to anti-TNFα therapy in IBD patients was identified as an expression quantitative trait loci for FAM114A2. FAM114A2 knockdown in macrophages led to increased TNFα secretion, potentially via an autophagy-mediated mechanism [4].

In summary, Fam114a2, while not essential for male fertility and spermatogenesis in mice, plays roles in cancer-related processes such as in bladder and cutaneous squamous cell carcinomas, and is associated with primary non-response to anti-TNFα therapy in IBD patients. The KO mouse model has been crucial in understanding its dispensability in spermatogenesis, and in vivo studies in cancer models have revealed its role in tumor progression. Overall, these findings contribute to understanding biological functions and disease mechanisms related to Fam114a2 [1,2,3,4].

References:

1. Khan, Asad, Yuewen, Wang, Dil, Sobia, Shi, Qinghua, Khan, Ranjha. 2021. The evolutionarily conserved gene, Fam114a2, is dispensable for fertility in mouse. In Reproductive biology, 21, 100531. doi:10.1016/j.repbio.2021.100531. https://pubmed.ncbi.nlm.nih.gov/34315090/

2. Liu, Tianyao, Lu, Qun, Liu, Jin, Guo, Hongqian, Yang, Rong. 2020. Circular RNA FAM114A2 suppresses progression of bladder cancer via regulating ∆NP63 by sponging miR-762. In Cell death & disease, 11, 47. doi:10.1038/s41419-020-2226-5. https://pubmed.ncbi.nlm.nih.gov/31969560/

3. Wei, X-H, Gu, X-L, Zhou, X-T, Ma, M, Lou, C-X. . miR-497 promotes the progression of cutaneous squamous cell carcinoma through FAM114A2. In European review for medical and pharmacological sciences, 22, 7348-7355. doi:10.26355/eurrev_201811_16272. https://pubmed.ncbi.nlm.nih.gov/30468480/

4. De, Tanima, Zhang, Honghong, Alarcon, Cristina, Parisiadou, Loukia, Perera, Minoli A. . Genetic association of primary nonresponse to anti-TNFα therapy in patients with inflammatory bowel disease. In Pharmacogenetics and genomics, 32, 1-9. doi:10.1097/FPC.0000000000000445. https://pubmed.ncbi.nlm.nih.gov/34380996/