Papillary thyroid carcinoma (PTC) is the prevalent histotype of thyroid cancer, with increasing incidence worldwide. MicroRNAs (miRNAs) could play an important role in the development and progression of human cancers. Interestingly, miR-326 was validated as one of the downregulated miRNAs in PTC. Therefore, it is necessary to research the function of miR-326 involved in the progression of PTC. In the current study, we detected the downregulation of miR-326 in PTC tissues and cell lines. The miR-326 overexpression or knockdown was conducted in TPC-1 or HTh83 PTC cells. miR-326 mimics decreased the proliferation, clone formation ability and caused G1-phase accumulation. In addition, the reduction of migration and invasion abilities was induced by miR-326 mimics. Western blot analysis showed that the cells with miR-326 mimics exhibited the inhibition of vimentin and N-cadherin, as well as enhancement of E-cadherin. Importantly, miR-326 could directly target mitogen activated protein kinase 1 (MAPK1) and epidermal growth factor receptor 4 (ERBB4). MAPK1 or ERBB4 overexpression rescued the effects of miR-326 on proliferation, migration, and invasion in PTC cells. Notably, miR-326 reduced tumorigenesis in vivo, including the decrease of tumor volume and weight, suppression of Ki-67, N-cadherin, MAPK1 and ERBB4. In all, these results might provide a new therapeutic target for the diagnosis of PTC.
Syntaxin-6 (STX6), a vesicular transport protein, is a direct target of the tumor suppressor gene P53, supporting cancer growth dependent on P53. However, STX6′s function in the tumor microenvironment has yet to be reported. In this research, we comprehensively explored the role of the oncogene STX6 in pan-cancer by combining data from several databases, including the Cancer Genome Atlas, CPTAC, cBioPortal, and TIMER. Then, we verified the carcinogenic effect of STX6 in hepatocellular carcinoma (HCC) and colorectal cancer (CRC) through a series of experiments in vitro and in vivo. Bioinformatics analysis demonstrated that STX6 is an oncogene for several cancers and is mainly involved in the cell cycle, epithelial–mesenchymal transition, oxidative phosphorylation, and tumor immune modulation, especially for tumor-associated fibroblasts (CAFs) and NKT cells. Additionally, a high level of STX6 could indicate patients’ resistance to immunotherapy. Our own data indicated that the STX6 level was upregulated in HCC and CRC. Knockdown of the STX6 levels could arrest the cell cycle and restrain cell proliferation, migration, and invasion. RNA-seq indicated that STX6 was significantly involved in pathways for cancer, such as the MAPK signal pathway. In a mouse model, knockdown of STX6 inhibited tumor growth and potentiated anti-PD-1 efficacy. In light of the essential roles STX6 plays in carcinogenesis and cancer immunology, it has the potential to be a predictive biomarker and a target for cancer immunotherapy.
Abstract. Point to problems of long tuning cycle and unapparent performance improvement in the chassis tuning process of keep changing suspension bushing parameters, considering the error of suspension installation, the robust optimization based on Taguchi method is proposed. Use Adams software to model suspension and by K&C test the accuracy of suspension. Utilize Isight software to analyze the degree of influence of bushing stiffness on suspension compliance characteristics. Adopt the Analytic Hierarchy Process method on the uniformity of objective function of suspension compliance characteristics. Design orthogonal experiment based on Taguchi Method to achieve suspension Pareto solution set. According to the best controllable factor, verify the optimization results by the Monte Carlo method. The result illustrated that both the suspension and robustness improved a lot after optimization.
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