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The recombinant human Keratin, type I cytoskeletal 19 I (KRT19) production is achieved through the manipulation of desired gene expression in baculovirus cells. The sequence (1-400aa) of foreign DNA is fused with the N-terminal 10xHis-tagged and C-terminal Myc-tag gene and then cloned into an expression vector, which is transformed into baculovirus cells. The positive cells are selected and cultured to induce the expression of the desired protein. The recombinant human KRT19 protein is subjected to affinity purification. Its purity is over 85%, as measured by SDS-PAGE.
KRT19 is a cytoplasmic intermediate filament protein that plays crucial roles in various cellular processes across different types of cancers. It is involved in cellular reprogramming, drug sensitivity, and aggressiveness of cancer stem cell-like cells [1]. KRT19 is also identified as a promising prognostic biomarker in serous ovarian cystadenocarcinoma and is associated with immune infiltrates in cancer [2]. In liver tumorigenesis, nuclear KRT19 acts as a transcriptional corepressor, promoting histone deacetylation and indicating poor prognosis in liver cancer [3]. Moreover, KRT19 is implicated in promoting the invasiveness of colorectal cancer by interacting with DIAPH3 [4].
Furthermore, KRT19 has been shown to regulate the cell cycle pathway and sensitivity of breast cancer cells to CDK inhibitors, emphasizing its role in breast cancer progression [5]. It directly interacts with the β-catenin/RAC1 complex to regulate the NUMB-dependent NOTCH signaling pathway in breast cancer [6]. Additionally, KRT19 is epigenetically silenced in certain cells but can be re-expressed after treatment with demethylating agents [7].
In hepatocellular carcinomas, KRT19 is a key player in invasion and is expressed in a subset of HCCs with poor prognosis [8]. Its expression is closely related to immune infiltration and can be used to predict breast cancer prognosis when combined with immune infiltration analysis [9]. Moreover, KRT19 is utilized as a marker for the regeneration of intrahepatic bile ducts in biliary atresia-specific deciduous pulp stem cells [10].
References:
[1] S. Saha, K. Kim, G. Yang, H. Choi, & S. Cho, Cytokeratin 19 (krt19) has a role in the reprogramming of cancer stem cell-like cells to less aggressive and more drug-sensitive cells, International Journal of Molecular Sciences, vol. 19, no. 5, p. 1423, 2018. https://doi.org/10.3390/ijms19051423
[2] Z. Sun, Krt19 is a promising prognostic biomarker and associates with immune infiltrates in serous ovarian cystadenocarcinoma, International Journal of General Medicine, vol. Volume 16, p. 4849-4862, 2023. https://doi.org/10.2147/ijgm.s419235
[3] S. Han, Nuclear krt19 is a transcriptional corepressor promoting histone deacetylation and liver tumorigenesis, Hepatology, 2024. https://doi.org/10.1097/hep.0000000000000875
[4] S. Mi, M1a-regulated diaph3 promotes the invasiveness of colorectal cancer via stabilization of krt19,, 2023. https://doi.org/10.21203/rs.3.rs-3350465/v1
[5] P. Sharma, S. Alsharif, K. Bursch, S. Parvathaneni, D. Anastasakis, J. Chahineet al., Keratin 19 regulates cell cycle pathway and sensitivity of breast cancer cells to cdk inhibitors, Scientific Reports, vol. 9, no. 1, 2019. https://doi.org/10.1038/s41598-019-51195-9
[6] S. Saha, H. Choi, K. Bw, D. Aa, G. Yang, K. Kset al., Krt19 directly interacts with β-catenin/rac1 complex to regulate numb-dependent notch signaling pathway and breast cancer properties, Oncogene, vol. 36, no. 3, p. 332-349, 2016. https://doi.org/10.1038/onc.2016.221
[7] C. Loriot, M. Domingues, A. Berger, M. Menara, M. Ruel, A. Morinet al., Deciphering the molecular basis of invasiveness in sdhb-deficient cells, Oncotarget, vol. 6, no. 32, p. 32955-32965, 2015. https://doi.org/10.18632/oncotarget.5106
[8] O. Govaere, M. Komuta, J. Berkers, B. Spee, C. Janssen, F. Lucaet al., Keratin 19: a key role player in the invasion of human hepatocellular carcinomas, Gut, vol. 63, no. 4, p. 674-685, 2013. https://doi.org/10.1136/gutjnl-2012-304351
[9] L. Mi, N. Liang, & H. Sun, A comprehensive analysis of krt19 combined with immune infiltration to predict breast cancer prognosis, Genes, vol. 13, no. 10, p. 1838, 2022. https://doi.org/10.3390/genes13101838
[10] S. Sonoda, K. Yoshimaru, H. Yamaza, R. Yuniartha, T. Matsuura, E. Yamauchi-Tomodaet al., Biliary atresia-specific deciduous pulp stem cells feature biliary deficiency, Stem Cell Research & Therapy, vol. 12, no. 1, 2021. https://doi.org/10.1186/s13287-021-02652-8
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