Gja10, encoding connexin-62 (Cx62 in humans, Cx57 in mice), is a gene that codes for connexins which are building blocks of gap-junctions and hemichannels. These structures are involved in intercellular communication, allowing the direct metabolic and electrical coupling between adjacent cells [2,3,8]. Gap-junctions and hemichannels play crucial roles in various biological processes such as the function of the retina and platelet function [2,8].

In the context of breast cancer, a long non-coding RNA lnc-GJA10-12:1 was identified as potentially regulating sentinel lymph node metastasis. It may act via targeting microRNAs like miR-34a-5p and miR-449a to regulate MAP2K1 and MAP3K9 expression levels, thus affecting the PI3K/Akt and MAPK signaling pathways [1]. In bats, the Gja10 gene has become a pseudogene in some species, providing evidence for a genetic-level trade-off between vision and echolocation as Gja10 is expressed abundantly in mammalian retinal horizontal cells and is important for horizontal cell coupling [4]. In gastric cancer, high GJA10 mRNA expression levels were associated with a poorer patient outcome [5]. In colorectal cancer, GJA10 was among the genes differentially expressed between hot and cold tumors, potentially serving as an immune-related prognostic target [6]. In goats, GJA10 was selected as a candidate gene for litter size through whole-genome re-sequencing, suggesting its possible role in fecundity-related processes [7].

In conclusion, Gja10 plays essential roles in multiple biological processes and diseases. Its functions range from intercellular communication in normal physiological conditions to being involved in disease-related pathways such as cancer metastasis and immune-related prognosis, as well as in the evolution-related sensory trade-off in bats. Research on Gja10 using various models has provided insights into these diverse biological functions and disease associations.

References:

1. Sun, Desheng, Zhong, Jieyu, Wei, Wei, Liu, Jun, Lin, Xiaona. 2020. Long non-coding RNAs lnc-ANGPTL1-3:3 and lnc-GJA10-12:1 present as regulators of sentinel lymph node metastasis in breast cancer. In Oncology letters, 20, 188. doi:10.3892/ol.2020.12050. https://pubmed.ncbi.nlm.nih.gov/32952657/

2. Klaassen, Lauw J, Fahrenfort, Iris, Kamermans, Maarten. 2012. Connexin hemichannel mediated ephaptic inhibition in the retina. In Brain research, 1487, 25-38. doi:10.1016/j.brainres.2012.04.059. https://pubmed.ncbi.nlm.nih.gov/22796289/

3. Söhl, Goran, Joussen, Antonia, Kociok, Norbert, Willecke, Klaus. 2010. Expression of connexin genes in the human retina. In BMC ophthalmology, 10, 27. doi:10.1186/1471-2415-10-27. https://pubmed.ncbi.nlm.nih.gov/20979653/

4. Shen, Bin, Fang, Tao, Dai, Mengyao, Jones, Gareth, Zhang, Shuyi. 2013. Independent losses of visual perception genes Gja10 and Rbp3 in echolocating bats (Order: Chiroptera). In PloS one, 8, e68867. doi:10.1371/journal.pone.0068867. https://pubmed.ncbi.nlm.nih.gov/23874796/

5. Zhao, Xuan, Yu, Chaoran, Zheng, Minhua, Sun, Jing. 2019. Prognostic value of the mRNA expression of gap junction α members in patients with gastric cancer. In Oncology letters, 18, 1669-1678. doi:10.3892/ol.2019.10516. https://pubmed.ncbi.nlm.nih.gov/31423234/

6. Wen, Huijuan, Li, Fazhan, Bukhari, Ihtisham, Zheng, Pengyuan, Liu, Simeng. 2022. Comprehensive Analysis of Colorectal Cancer Immunity and Identification of Immune-Related Prognostic Targets. In Disease markers, 2022, 7932655. doi:10.1155/2022/7932655. https://pubmed.ncbi.nlm.nih.gov/35401882/

7. Wang, Ke, Liu, Xinfeng, Qi, Tang, Lan, Xianyong, Pan, Chuanying. 2020. Whole-genome sequencing to identify candidate genes for litter size and to uncover the variant function in goats (Capra hircus). In Genomics, 113, 142-150. doi:10.1016/j.ygeno.2020.11.024. https://pubmed.ncbi.nlm.nih.gov/33276007/

8. Sahli, Khaled A, Flora, Gagan D, Sasikumar, Parvathy, McGuffin, Liam J, Gibbins, Jonathan M. . Structural, functional, and mechanistic insights uncover the fundamental role of orphan connexin-62 in platelets. In Blood, 137, 830-843. doi:10.1182/blood.2019004575. https://pubmed.ncbi.nlm.nih.gov/32822477/