Beta-actin (ACTB), a highly conserved cytoskeleton structural protein, has been regarded as a common housekeep gene and used as a reference gene for years. However, accumulating evidence indicates that ACTB is abnormally expressed in multiple cancers and hence changes the cytoskeleton to affect the invasiveness and metastasis of tumors. This study aimed to investigate the function and clinical significance of ACTB in pan-cancer. The role of ACTB for prognosis and immune regulation across 33 tumors was explored based on the datasets of gene expression omnibus and the cancer genome atlas. Differential expression of ACTB was found between cancer and adjacent normal tissues, and significant associations was found between ACTB expression and prognosis of tumor patients. In most cancers, ACTB expression was associated with immune cells infiltration, immune checkpoints and other immune modulators. Relevance between ACTB and metastasis and invasion was identified in various types of cancers by CancerSEA. Moreover, focal adhesion and actin regulation-associated pathways were included in the functional mechanisms of ACTB. The expression of ACTB was verified by quantitative real-time polymerase chain reaction. Knockdown of ACTB inhibited head and neck squamous carcinoma cell migration and invasion by NF-κB and Wnt/β-catenin pathways. Our first pan-cancer study of ACTB offers insight into the prognostic and immunological roles of ACTB across different tumors, indicating ACTB may be a potential biomarker for poor prognosis and immune infiltration in cancers, and the role of ACTB as a reference gene in cancers was challenged.

Inadequate oxygen supply is probably one of the most important pathophysiological mechanisms of cardiomyocyte damage in ischemic heart disease. Tetramethylpyrazine (TMP, also known as ligustrazine) is the main active ingredient isolated from the rhizome of Ligusticum chuanxiong Hort. A previous study reported that the TMP could exert cardioprotective activity. This study aimed to explore the molecular mechanism of the protective effects of TMP on cardiomyocyte damage caused by hypoxia. The viability and apoptosis of cardiomyocytes H9c2 were detected using cell counting kit‐8 assay and annexin V‐FITC/PI staining, respectively. Quantitative reverse transcription polymerase chain reaction was conducted to measure the expression level of microRNA‐449a (miR‐449a). Cell transfection was performed to upregulate the expression level of miR‐449a or downregulate the expression level of sirtuin 1 (Sirt1). The protein expression levels of Sirt1 and key factors involved in cell apoptosis and phosphatidylinositol 3‐kinase/protein kinase 3 (PI3K/AKT) pathway were evaluated using western blot analysis. We found that the hypoxia incubation inhibited H9c2 viability, induced cell apoptosis, and inactivated the PI3K/AKT pathway. TMP treatment partially relieved the hypoxia‐caused H9c2 cell viability loss and apoptosis, as well as reversed the hypoxia‐caused inactivation of the PI3K/AKT pathway. Moreover, TMP partially alleviated the upregulation of miR‐449a in H9c2 cells caused by hypoxia. Overexpression of miR‐449a weakened the effects of TMP on hypoxia‐treated H9c2 cells. Furthermore, Sirt1 was a target gene of miR‐449a. Knockdown of Sirt1 also weakened the effects of TMP on hypoxia‐treated H9c2 cells. In conclusion, TMP partially relieved hypoxia‐caused cardiomyocytes H9c2 viability loss and apoptosis at least through downregulating miR‐499a, upregulating Sirt1, and then activating the PI3K/AKT pathway.

Head and neck squamous carcinoma (HNSC) is a frequent and deadly malignancy that is challenging to manage. The existing treatment options have considerable efficacy limitations. Hence, the identification of new therapeutic targets and the development of efficacious treatments are urgent needs. Cuproptosis, a non-apoptotic programmed cell death caused by excess copper, has only very recently been discovered. The present study investigated the prognostic importance of genes involved in cuproptosis through the mRNA expression data and related clinical information of HNSC patients downloaded from public databases. Our results revealed that many cuproptosis-related genes were differentially expressed between normal and HNSC tissues in the TCGA cohort. Moreover, 39 differentially expressed genes were associated with the prognosis of HNSC patients. Then, a 24-gene signature was identified in the TCGA cohort utilizing the LASSO Cox regression model. HNSC expression data used for validation were obtained from the GEO database. Consequently, we divided patients into high- and low-risk groups based on the 24-gene signature. Furthermore, we demonstrated that the high-risk group had a worse prognosis when compared to the low-risk group. Additionally, significant differences were found between the two groups in metabolic pathways, immune microenvironment, etc. In conclusion, we found a cuproptosis-related gene signature that can be used effectively to predict OS in HNSC patients. Thus, targeting cuproptosis might be an alternative and promising strategy for HNSC patients.