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Objective To investigate the effect of high keratin 23 （KRT23） expression promoting cell proliferation on liver cancer. Methods The expression of KRT23 in liver cancer was analyzed by bioinformatics. After overexpression and inhibition of KRT23， the effect of KRT23 on the proliferation of liver cancer cells was analyzed by MTT and clone formation assay. The regulatory relationship between KRT23 and AKT signaling pathway was analyzed by software prediction， qPCRand Western blot. Results The expression level of KRT23 in liver cancer was significantly higher than that in normal control tissues. MTT and clone formation assay showed that overexpression of KRT23 promoted cell proliferation， while downregulation of KRT23 inhibited cell proliferation. GSEA analysis， qPCR and Western blot showed that KRT23 could activate the AKT signaling pathway and promote cell proliferation. Meanwhile， inhibition of AKT signaling pathway in overexpressing KRT23 cells significantly reduced cell proliferation. Conclusions KRT23 affects the proliferation of liver cancer cells by regulating the AKT signaling pathway. These results suggest that KRT23 exerts significant effects upon the malignant procession of liver cancer and may play an important role in the occurrence and development of liver cancer.

Objective To investigate the effect of high keratin 23 (KRT23) expression promoting cell proliferation on liver cancer. Methods The expression of KRT23 in liver cancer was analyzed by bioinformatics. After overexpression and inhibition of KRT23, the effect of KRT23 on the proliferation of liver cancer cells was analyzed by MTT and clone formation assay. The regulatory relationship between KRT23 and AKT signaling pathway was analyzed by software prediction, qPCRand Western blot. Results The expression level of KRT23 in liver cancer was significantly higher than that in normal control tissues. MTT and clone formation assay showed that overexpression of KRT23 promoted cell proliferation, while downregulation of KRT23 inhibited cell proliferation. GSEA analysis, qPCR and Western blot showed that KRT23 could activate the AKT signaling pathway and promote cell proliferation. Meanwhile, inhibition of AKT signaling pathway in overexpressing KRT23 cells significantly reduced cell proliferation. Conclusions KRT23 affects the proliferation of liver cancer cells by regulating the AKT signaling pathway. These results suggest that KRT23 exerts significant effects upon the malignant procession of liver cancer and may play an important role in the occurrence and development of liver cancer. [ABSTRACT FROM AUTHOR]

Cervical cancer (CC) is one of the most common malignancies in women worldwide. Dismal prognosis rates have been associated with conventional therapeutic approaches, emphasizing the need for new strategies. Recently, immunotherapy has been used to treat various types of solid tumors, and different subtypes of the tumor microenvironment (TME) are associated with diverse responses to immunotherapy. Accordingly, understanding the complexity of the TME is pivotal for immunotherapy. Herein, we used two methods, "ssGSEA" and "xCell," to identify the immune profiles in CC and comprehensively assess the relationship between immune cell infiltration and genomic alterations. We found that more adaptive immune cells were found infiltrated in tumor tissues than in normal tissues, whereas the opposite was true for innate cells. Consensus clustering of CC samples based on the number of immune cells identified four clusters with different survival and immune statuses. Then, we subdivided the above four clusters into "hot" and "cold" tumors, where hot tumors exhibited higher immune infiltration and longer survival time. Enrichment analyses of differentially expressed genes (DEGs) revealed that the number of activated immune signaling pathways was higher in hot tumors than that in cold tumors. Keratin, type I cytoskeletal 23 (KRT23), was upregulated in cold tumors and negatively correlated with immune cell infiltration. In vitro experiments, real-time reverse transcription-quantitative polymerase chain reaction, cytometric bead arrays, and ELISA revealed that knockdown of KRT23 expression could promote the secretion of C-C motif chemokine ligand-5 and promote the recruitment of CD8+ T cells. We also constructed a model based on DEGs that exhibited a high predictive power for the survival of CC patients. Overall, our study provides deep insights into the immune cell infiltration patterns of CC. Moreover, KRT23 has huge prospects for application as an immunotherapeutic target. Finally, our model demonstrated a good predictive power for the prognosis of CC patients and may guide clinicians during immunotherapy. [ABSTRACT FROM AUTHOR]

Cervical cancer (CC) is one of the most common malignancies in women worldwide. Dismal prognosis rates have been associated with conventional therapeutic approaches, emphasizing the need for new strategies. Recently, immunotherapy has been used to treat various types of solid tumors, and different subtypes of the tumor microenvironment (TME) are associated with diverse responses to immunotherapy. Accordingly, understanding the complexity of the TME is pivotal for immunotherapy. Herein, we used two methods, “ssGSEA” and “xCell,” to identify the immune profiles in CC and comprehensively assess the relationship between immune cell infiltration and genomic alterations. We found that more adaptive immune cells were found infiltrated in tumor tissues than in normal tissues, whereas the opposite was true for innate cells. Consensus clustering of CC samples based on the number of immune cells identified four clusters with different survival and immune statuses. Then, we subdivided the above four clusters into “hot” and “cold” tumors, where hot tumors exhibited higher immune infiltration and longer survival time. Enrichment analyses of differentially expressed genes (DEGs) revealed that the number of activated immune signaling pathways was higher in hot tumors than that in cold tumors. Keratin, type I cytoskeletal 23 (KRT23), was upregulated in cold tumors and negatively correlated with immune cell infiltration. In vitro experiments, real-time reverse transcription-quantitative polymerase chain reaction, cytometric bead arrays, and ELISA revealed that knockdown of KRT23 expression could promote the secretion of C-C motif chemokine ligand-5 and promote the recruitment of CD8+ T cells. We also constructed a model based on DEGs that exhibited a high predictive power for the survival of CC patients. Overall, our study provides deep insights into the immune cell infiltration patterns of CC. Moreover, KRT23 has huge prospects for application as an immunotherapeutic target. Finally, our model demonstrated a good predictive power for the prognosis of CC patients and may guide clinicians during immunotherapy.

Abstract: Transcript profiling of 27 normal colon mucosas and 258 adenocarcinomas showed Keratin23 to be increased in 78% microsatellite-stable tumors, while microsatellite-instable tumors showed low transcript levels, comparable to normal mucosas. Immunohistochemical analyses demonstrated that 88% of microsatellite-instable tumors were negative for Keratin23 protein, while 70% of MSS tumors and metastases derived from MSS-tumors showed high Keratin23 levels. Immunofluorescence analysis localized Keratin23 in the Golgi-apparatus. Golgi accumulation was unique for gastrointestinal adenocarcinomas. Immunoprecipitation and 2D-blot analysis revealed Keratin23 to be a 46.8kDa phosphoprotein. Keratin23 impaired the proliferation of human colon cancer cells significantly, leading to cell death in microsatellite-instable but not microsatellite-stable cell lines, while COS7 cells experienced multiple nuclei and apoptosis. Keratin23 expression correlated significantly with transcription factor CEBPB. In conclusion, Keratin23 expression is a novel and important difference between microsatellite-stable and microsatellite-instable colon cancers. [Copyright &y& Elsevier]