Cbll1, also known as Hakai, is an E3 ubiquitin ligase. It is involved in the ubiquitination, endocytosis, and degradation of E-cadherin, regulating cell proliferation. Additionally, it is one of the m6A methyltransferases that modify eukaryotic RNAs, which is crucial for various physiological and pathological processes [1,5].

In recurrent spontaneous abortion (RSA), CBLL1 is upregulated in the decidua of RSA patients. Overexpression of CBLL1 in human endometrial stromal cells promotes cell senescence, increases oxidative stress, and inhibits proliferation by inhibiting PTEN, and in vivo experiments in mice show it causes a higher embryo absorption rate [2].

In non-small cell lung cancer (NSCLC), CBLL1 is frequently upregulated. It promotes cell proliferation by facilitating the G1/S cell cycle transition and promotes invasion. Knockdown of CBLL1 inhibits invasion via increasing E-cadherin protein expression and decreasing MMP2 and MMP9 expression [3].

In colorectal cancer, CBLL1 gene expression is specifically associated with the canonical subtype CMS2. High CBLL1 expression in CMS2 patients is related to worse overall survival [4].

In conclusion, CBLL1 plays important roles in multiple disease conditions such as recurrent spontaneous abortion, non-small cell lung cancer, and colorectal cancer. Its functions mainly revolve around cell proliferation, senescence, and invasion, which are revealed through in vivo studies including mouse models in relevant research. Understanding CBLL1 can provide insights into the mechanisms of these diseases and potential therapeutic targets.