CRSP8 plays an important role in recruiting mediators to genes through direct interaction with various DNA-bound transactivators. In this study, we uncovered the unique function of CRSP8 in suppressing thyroid cancer differentiation and promoting thyroid cancer progression via targeting IKKα signaling. CRSP8 was highly expressed in human thyroid cancer cells and tissues, especially in anaplastic thyroid cancer (ATC). Knockdown of CRSP8 suppressed cell growth, migration, invasion, stemness, and induced apoptosis and differentiation in ATC cells, while its overexpression displayed opposite effects in differentiated thyroid cancer (DTC) cells. Mechanistically, CRSP8 downregulated IKKα expression by binding to the IKKα promoter region (−257 to −143) to negatively regulate its transcription. Knockdown or overexpression of IKKα significantly reversed the expression changes of the differentiation and EMT-related markers and cell growth changes mediated by CRSP8 knockdown or overexpression in ATC or DTC cells. The in vivo study also validated that CRSP8 knockdown inhibited the growth of thyroid cancer by upregulating IKKα signaling in a mouse model of human ATC. Furthermore, we found that CRSP8 regulated the sensitivity of thyroid cancer cells to chemotherapeutics, including cisplatin and epirubicin. Collectively, our results demonstrated that CRSP8 functioned as a modulator of IKKα signaling and a suppressor of thyroid cancer differentiation, suggesting a potential therapeutic strategy for ATC by targeting CRSP8/IKKα pathway.
Colorectal cancer (CRC) is continuously rising among young adult patients, necessitating more forethoughtful study and understanding of the mechanisms behind CRC and the development of the new diagnostic and therapeutic strategies. Our research demonstrated that SPT6 synergized with staphylococcal nuclease and Tudor domain containing 1 (SND1) to promote CRC progression by targeting human telomerase reverse transcriptase (hTERT) and put forward that inhibiting SPT6‐SND1‐hTERT axis may create a therapeutic vulnerability in CRC.
In this paper, adopting the small scale model experimental method, made the test pile with half and whole cross-section, and through the homemade soil device to extract the undisturbed soil to carry out the load experiment. Observe the failure process of the soil around the pile body, at the same time, extract the load and displacement of the top of pile to form the curve. Finally, by comparing the the soil failure state 、bearing capacity 、the displacement-load curve of the half and whole cross-section piles and so on, further verify the reliability of the half cross-section pile experiment, set good theoretical and practical basis for the further promotion of half section pile experiment.
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