Fam53b, also known as Simplet, is a gene belonging to a family of vertebrate-specific genes. It is crucial for cell proliferation, as it can bind to 14-3-3 chaperones and SKIIP proteins [7]. It is involved in the canonical β-catenin-dependent Wnt signal transduction pathway by positively regulating β-catenin nuclear localization, which is important for cell fate determination, cell proliferation, stem cell maintenance and anterior-posterior axis formation [4].

In papillary thyroid carcinoma, circ_FAM53B (a circular RNA related to Fam53b) expression is reduced, and it restrains cell proliferation, migration, invasion, and triggers apoptosis. It acts through the miR-183-5p-CCDC6 axis [1]. In pancreatic ductal adenocarcinoma, FAM53B promotes metastasis by regulating macrophage M2 polarization [2]. In acute lymphoblastic leukemia, a chromosome translocation can cause a truncation of FAM53B [3]. In ovarian cancer, circ-FAM53B is overexpressed and accelerates cancer progression via the miR-646/VAMP2 and miR-647/MDM2 signaling pathways [5]. Father's preconception smoking, especially in puberty, is associated with offspring DNA methylation of FAM53B, which is related to offspring outcomes like weight, BMI, asthma and wheezing [6]. Also, FAM53B has been identified as a risk gene for cocaine dependence [8], and there are smoking-informed methylation and expression QTLs related to it in the human brain [9].

In summary, Fam53b and its related circular RNAs play significant roles in multiple biological processes and disease conditions. Through studies in various disease models, we have learned that it is involved in cell proliferation, Wnt signaling, and can influence cancer development, metastasis, and even has an association with offspring health related to parental smoking. These findings provide insights into potential therapeutic and prevention strategies for relevant diseases.

References:

1. Zhang, Chong, Gu, Huxia, Liu, Dingrong, Dai, Xiaolu, Tian, Haibo. 2022. The circ_FAM53B-miR-183-5p-CCDC6 axis modulates the malignant behaviors of papillary thyroid carcinoma cells. In Molecular and cellular biochemistry, 477, 2627-2641. doi:10.1007/s11010-022-04465-6. https://pubmed.ncbi.nlm.nih.gov/35598218/

2. Pei, Xuan-Zeng, Cai, Min, Jiang, Da-Wei, Lu, Hui-Min, Lu, Yi-Fan. . FAM53B promotes pancreatic ductal adenocarcinoma metastasis by regulating macrophage M2 polarization. In World journal of gastrointestinal oncology, 16, 1479-1499. doi:10.4251/wjgo.v16.i4.1479. https://pubmed.ncbi.nlm.nih.gov/38660645/

3. Panagopoulos, Ioannis, Gorunova, Ludmila, Torkildsen, Synne, Heim, Sverre, Micci, Francesca. 2017. FAM53B truncation caused by t(10;19)(q26;q13) chromosome translocation in acute lymphoblastic leukemia. In Oncology letters, 13, 2216-2220. doi:10.3892/ol.2017.5705. https://pubmed.ncbi.nlm.nih.gov/28454383/

4. Kizil, Caghan, Küchler, Beate, Yan, Jia-Jiun, Weidinger, Gilbert, Antos, Christopher L. . Simplet/Fam53b is required for Wnt signal transduction by regulating β-catenin nuclear localization. In Development (Cambridge, England), 141, 3529-39. doi:10.1242/dev.108415. https://pubmed.ncbi.nlm.nih.gov/25183871/

5. Sun, Dan, Liu, Jianing, Zhou, Lili. 2019. Upregulation of circular RNA circ‑FAM53B predicts adverse prognosis and accelerates the progression of ovarian cancer via the miR‑646/VAMP2 and miR‑647/MDM2 signaling pathways. In Oncology reports, 42, 2728-2737. doi:10.3892/or.2019.7366. https://pubmed.ncbi.nlm.nih.gov/31638250/

6. Kitaba, Negusse Tadesse, Knudsen, Gerd Toril Mørkve, Johannessen, Ane, Svanes, Cecilie, Holloway, John W. 2023. Fathers' preconception smoking and offspring DNA methylation. In Clinical epigenetics, 15, 131. doi:10.1186/s13148-023-01540-7. https://pubmed.ncbi.nlm.nih.gov/37649101/

7. Thermes, Violette, Candal, Eva, Alunni, Alessandro, Bourrat, Franck, Joly, Jean-Stéphane. 2006. Medaka simplet (FAM53B) belongs to a family of novel vertebrate genes controlling cell proliferation. In Development (Cambridge, England), 133, 1881-90. doi:. https://pubmed.ncbi.nlm.nih.gov/16611694/

8. Gelernter, J, Sherva, R, Koesterer, R, Kranzler, H R, Farrer, L. 2013. Genome-wide association study of cocaine dependence and related traits: FAM53B identified as a risk gene. In Molecular psychiatry, 19, 717-23. doi:10.1038/mp.2013.99. https://pubmed.ncbi.nlm.nih.gov/23958962/

9. Carnes, Megan Ulmer, Quach, Bryan C, Zhou, Linran, Johnson, Eric O, Hancock, Dana B. 2024. Smoking-informed methylation and expression QTLs in human brain and colocalization with smoking-associated genetic loci. In Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 49, 1749-1757. doi:10.1038/s41386-024-01885-4. https://pubmed.ncbi.nlm.nih.gov/38830989/