Cbll1, also known as Hakai, is an E3 ubiquitin ligase. It is involved in the ubiquitination, endocytosis, and degradation of epithelial cadherin (E-cadherin), thus regulating cell proliferation [5]. It is also one of the m6A methyltransferases, participating in the m6A modification process of eukaryotic RNAs, which is crucial for various physiological and pathological processes [1].

In recurrent spontaneous abortion (RSA), CBLL1 is upregulated in the decidua of RSA patients. Overexpression of CBLL1 promotes endometrial stromal cell senescence, increases oxidative stress levels, and inhibits proliferation by inhibiting PTEN [2]. In non-small cell lung cancer (NSCLC), CBLL1 is frequently upregulated, and its high expression is associated with tumor size. CBLL1 promotes cell proliferation by facilitating G1/S cell cycle transition and promotes invasion by regulating E-cadherin, MMP2, and MMP9 expression [3]. In colorectal cancer, CBLL1 gene expression is specifically associated with canonical subtype CMS2, and high CBLL1 expression in CMS2 patients is associated with worse overall survival [4].

In conclusion, CBLL1 plays important roles in multiple biological processes and disease conditions. Its functions in cell proliferation, senescence, and invasion, as revealed through in-vivo and functional studies, are crucial in understanding diseases such as RSA, NSCLC, and colorectal cancer. The study of CBLL1 provides potential targets for the treatment of these diseases.

References:

1. Jiang, Xiulin, Liu, Baiyang, Nie, Zhi, Yang, Cuiping, Chen, Yongbin. 2021. The role of m6A modification in the biological functions and diseases. In Signal transduction and targeted therapy, 6, 74. doi:10.1038/s41392-020-00450-x. https://pubmed.ncbi.nlm.nih.gov/33611339/

2. Liu, Xueqing, Wei, Xiaowei, Wu, Jiayi, Chen, Cailian, Lin, Yi. . CBLL1 promotes endometrial stromal cell senescence via inhibiting PTEN in recurrent spontaneous abortion. In FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 38, e23833. doi:10.1096/fj.202400972R. https://pubmed.ncbi.nlm.nih.gov/39012313/

3. Hui, Linping, Zhang, Siyang, Wudu, Muli, Zhang, Qingfu, Qiu, Xueshan. 2019. CBLL1 is highly expressed in non-small cell lung cancer and promotes cell proliferation and invasion. In Thoracic cancer, 10, 1479-1488. doi:10.1111/1759-7714.13097. https://pubmed.ncbi.nlm.nih.gov/31124298/

4. Alfonsín, Gloria, Berral-González, Alberto, Rodríguez-Alonso, Andrea, De Las Rivas, Javier, Figueroa, Angélica. 2024. Stratification of Colorectal Patients Based on Survival Analysis Shows the Value of Consensus Molecular Subtypes and Reveals the CBLL1 Gene as a Biomarker of CMS2 Tumours. In International journal of molecular sciences, 25, . doi:10.3390/ijms25031919. https://pubmed.ncbi.nlm.nih.gov/38339195/

5. Fan, Dongmei, Xie, Xiaojuan, Qi, Pengwei, Yang, Xianan, Jin, Ximeng. 2017. Human mesenchymal stem cell homing induced by SKOV3 cells. In American journal of translational research, 9, 230-246. doi:. https://pubmed.ncbi.nlm.nih.gov/28337256/