ABSTRACT
OBJECTIVE: Recent studies indicated that transmembrane protein 40 (TMEM40) is associated with several types of cancers but is not clear in cervical cancer (CC). The study aimed to examine the role of TMEM40 in CC and related mechanisms. METHODS: The expression of TMEM40 in CC tissues and cell lines was studied with western blot and real-time quantitative RT-PCR. The effect of TMEM40 on proliferation was evaluated by CCK-8, EdU and colony formation assay. The migration, invasion, cell cycle and apoptosis of CC cells were studied with wound healing, transwell assays and flow cytometry. Tumor growth was evaluated in vivo using a xenogenous subcutaneously implant model. RESULTS: The results revealed that the TMEM40 elevation in CC tissues and cell lines was closely correlated with tumor size and lymph node metastasis in clinical patients. Upregulation of TMEM40 with OE-TMEM40 vector promoted the invasion, migration and proliferation, inhibited the apoptosis and led to distinct S cell cycle arrest in CC cell lines. Silencing TMEM40 with shRNA inhibited the invasion, migration and proliferation, promoted apoptosis and led to a G0/G1 cell cycle arrest in CC cell lines. Silence of TMEM40 downregulated the expression of c-MYC, Cyclin D1, matrix metalloproteinase-1 (MMP-1) and matrix metalloproteinase-9 (MMP-9), but in contrast, activated p53 and several apoptosis related proteins such as p53, Caspase-3, Caspase-9 and PARP1. In addition, TMEM40 silencing dramatically decreased tumor growth in mice models. CONCLUSION: The present study demonstrates that TMEM40 upregulation can be a potential prognostic biomarker and contribute to CC development.
ABSTRACT
With the development of new energy vehicles, the joining of lightweight alloys has received more attention. Self-piercing riveting experiments of aluminum alloy and high-strength steel sheets were performed to analyze the effects of rivet height and laying order of metal sheets on the joining quality in the work. The forming surface, cross-sectional morphology, static tensile property, fatigue property, failure mode, and mechanism were analyzed. The results show that AA5052 alloy and SPFC440 steel can be joined effectively by self-piercing riveting, and there is good contact between rivet head and sheet surfaces. When the rivet is 2.5-3.5 mm higher than the total thickness of two layers sheets, the rivet leg flares symmetrically without cracks or buckling, and the lower sheet completely encapsulates the joint button. The joints have better static tensile properties when the rivet is about 3 mm higher than the thickness of two sheets. The higher static strength is obtained when the aluminum alloy is placed at the lower position. The rivet legs fall off from the lower sheets for all the samples in the tensile tests, which is independent of the rivet height and laying order of metal sheets. The fatigue strength of the sample with the rivet height of 7 mm is the greatest, and the fatigue cracks always occur on the aluminum sheet under all experimental conditions. The findings in this work can help the practical application of self-piercing riveting for aluminum/steel sheets.
