Actb-KO Mouse

Actb, also known as beta-actin, is a highly conserved cytoskeleton structural protein. It has long been regarded as an endogenous housekeeping gene. Actin proteins are essential components of the cytoskeleton, playing a crucial role in maintaining cell structure, cell motility, and cell division. They are also involved in pathways related to focal adhesion and actin regulation [2].

Actb is closely associated with a variety of cancers. In most tumor cells and tissues, it is generally up-regulated. Its abnormal expression and polymerization, along with resulting cytoskeleton changes, are linked to cancer invasiveness and metastasis [1]. A pan-cancer analysis showed its differential expression between cancer and adjacent normal tissues, and its expression was associated with prognosis of tumor patients, immune cells infiltration, immune checkpoints, and other immune modulators in most cancers. Knockdown of Actb inhibited head and neck squamous carcinoma cell migration and invasion through NF-κB and Wnt/β-catenin pathways [2]. In hepatocellular carcinoma, mutant Actb mRNA 3'-UTR promotes cancer development by regulating miR-1 and miR-29a [5]. Also, in HBV-related early-stage hepatocellular carcinoma following partial hepatectomy, low Actb expression can predict a lower risk of recurrence with lenvatinib treatment [6]. Post-zygotic Actb mutations underlie congenital smooth muscle hamartomas, and are also detected in Becker's nevus patients, suggesting a possible genotype-phenotype correlation [3,4].

In conclusion, Actb is vital for maintaining normal cell functions through its role in the cytoskeleton. Studies, including those using potential gene knockout models implied by its functional studies, have revealed its significant association with multiple diseases, especially cancers. These findings provide insights into the molecular mechanisms of disease occurrence and potential biomarker discovery for prognosis and treatment response prediction in cancer [1,2,3,4,5,6].

References:

1. Guo, Chunmei, Liu, Shuqing, Wang, Jiasheng, Sun, Ming-Zhong, Greenaway, Frederick T. 2012. ACTB in cancer. In Clinica chimica acta; international journal of clinical chemistry, 417, 39-44. doi:10.1016/j.cca.2012.12.012. https://pubmed.ncbi.nlm.nih.gov/23266771/

2. Gu, Yuxi, Tang, Shouyi, Wang, Zhen, Shen, Yingqiang, Zhou, Yu. . A pan-cancer analysis of the prognostic and immunological role of β-actin (ACTB) in human cancers. In Bioengineered, 12, 6166-6185. doi:10.1080/21655979.2021.1973220. https://pubmed.ncbi.nlm.nih.gov/34486492/

3. Dai, Shangzhi, Wang, Huijun, Lin, Zhimiao. 2021. ACTB Mutations Analysis and Genotype-Phenotype Correlation in Becker's Nevus. In Biomedicines, 9, . doi:10.3390/biomedicines9121879. https://pubmed.ncbi.nlm.nih.gov/34944694/

4. Atzmony, Lihi, Ugwu, Nelson, Zaki, Theodore D, Antaya, Richard J, Choate, Keith A. 2020. Post-zygotic ACTB mutations underlie congenital smooth muscle hamartomas. In Journal of cutaneous pathology, 47, 681-685. doi:10.1111/cup.13683. https://pubmed.ncbi.nlm.nih.gov/32170967/

5. Li, Yong, Ma, Hongbin, Shi, Changying, Feng, Feiling, Yang, Liang. 2019. Mutant ACTB mRNA 3'-UTR promotes hepatocellular carcinoma development by regulating miR-1 and miR-29a. In Cellular signalling, 67, 109479. doi:10.1016/j.cellsig.2019.109479. https://pubmed.ncbi.nlm.nih.gov/31846694/

6. Dong, Wei, Zou, Minghao, Sheng, Jie, Liu, Hui, Dong, Hui. 2023. ACTB may serve as a predictive marker for the efficacy of lenvatinib in patients with HBV-related early-stage hepatocellular carcinoma following partial hepatectomy: a retrospective cohort study. In Journal of gastrointestinal oncology, 14, 2479-2499. doi:10.21037/jgo-23-942. https://pubmed.ncbi.nlm.nih.gov/38196518/