Background: Chemoresistance is one of the main causes of recurrence in colorectal cancer (CRC) patients and leads to a poor prognosis. To characterize RUNX1 expression in colorectal cancer (CRC) and elucidate its mechanistic involvement in the tumor biology of this disease. Methods: The expression of RUNX1 in CRC and normal tissues was detected by bioinformatics analysis. Cell proliferation was measured by CCK-8 and clonogenic assays. In vivo tumor progression was assessed with a xenograft mouse model. Cell drug sensitivity tests and flow cytometry were performed to analyze CRC cell chemoresistance. RUNX1, key molecules of the Hedgehog signaling pathway, and ABCG2 were detected by qRT-PCR and Western blotting. Results: RUNX1 expression is upregulated in CRC tissues. RUNX1 enhanced CRC cell resistance to 5-fluorouracil (5-FU), promoted proliferation, and inhibited 5-FU-induced apoptosis. Mechanistically, RUNX1 can activate the Hedgehog signaling pathway and promote the expression of ABCG2 in CRC cells. Conclusions: Our study demonstrated that RUNX1 promotes CRC proliferation and chemoresistance by activating the Hedgehog signaling pathway and ABCG2 expression.
Given the importance of student engagement for educational success, it is essential to explore how teachers can stimulate student engagement in online learning environment. However, relatively little research drawing from self-determination theory has examined the links between teaching motivations and student engagement. To this end, this study was conducted to survey 414 Chinese college students’ perceptions of teaching motivations, their own intrinsic and extrinsic motivations during the learning process, as well as their engagement with online learning. The findings indicated that the survey had satisfactory validity and internal consistency. Structural equation model revealed the interrelationships between autonomy-supportive teaching motivations, controlling teaching motivations, student intrinsic and extrinsic motivations, and student engagement. The results showed that in online learning environments, autonomy-supportive teaching motivations and student intrinsic motivation were positively related to student engagement. Unexpectedly, controlling teaching motivations and student extrinsic motivation had no significant effect on student engagement. Moreover, the mediating effects of student intrinsic motivation including perceived autonomy, competence, and relatedness offered a deeper understanding of the association between autonomy-supportive teaching motivations and student engagement. The main findings and practical implications together are discussed in depth. Implications for practice or policy: Teachers could adopt autonomy-supportive teaching strategies and stimulate students’ intrinsic motivation as they have shown to be positive factors for student engagement. Developers and educators could enhance student engagement through nurturing inner motivational resources in online learning environment. Researchers could verify more factors that influence student engagement and clarify how they could be manipulated in future studies.
DDX39B (also called UAP56 or BAT1) which is a kind of DEAD-box family helicase plays pivotal roles in mRNA binding, splicing, and export. It has been found upregulated in many kinds of tumors as an oncogene. Nevertheless, the underlying molecular mechanisms of DDX39B in the proliferation of human colorectal cancer (CRC) remain fairly elusive. In our study, function experiments including the CCK8 and colony formation assay revealed that DDX39B facilitates CRC proliferation in vitro. DDX39B knockdown cells were administered for the orthotopic CRC tumor xenograft mouse model, after which tumor growth was monitored and immunohistochemistry (IHC) was performed to prove that DDX39B can also facilitates CRC proliferation in vivo. Flow cytometry demonstrated that DDX39B promotes the proliferation of CRC cells by driving the cell cycle from G0/G1 phase to the S phase. Mechanistically, RNA-binding protein immunoprecipitation-sequencing (RIP-seq) confirmed that DDX39B binds directly to the first exon of the CDK6/CCND1 pre-mRNA and upregulates their expression. Splicing experiments in vitro using a RT-PCR and gel electrophoresis assay confirmed that DDX39B promotes CDK6/CCND1 pre-mRNA splicing. Rescue experiments indicated that CDK6/CCND1 is a downstream effector of DDX39B-mediated CRC cell proliferation. Collectively, our results demonstrated that DDX39B and CDK6/CCND1 direct interactions serve as a CRC proliferation promoter, which can accelerate the G1/S phase transition to enhance CRC proliferation, and can offer novel and emerging treatment strategies targeting this cell proliferation-promoting gene.
Background X-linked retinoschisis (XLRS), due to mutations in the RS1 gene, is a common genetically determined form of macular degeneration. This report describes an unusual case of angle-closure glaucoma (ACG) with XLRS and discusses the treatment. Case presentation A 39-year-old Chinese man with an X chromosome-recessive inherited c.489G > A variant in the RS1 gene was diagnosed as XLRS and ACG, presenting with cystic macular lesions, shallow anterior chamber depth (ACD), and angle-closure with uncontrolled intraocular pressure (IOP). Malignant glaucoma occurred following trabeculectomy combining phacoemulsification with intraocular lens (IOL) implantation and goniosynechialysis. Subsequent anterior vitrectomy and irido-zonulo-hyaloid-vitrectomy (IZHV) effectively lowered IOP and deepened ACD, but the cystic cavity became larger. Conclusions There is a potential risk of malignant glaucoma in ACG patients with XLRS after filtering surgery. Although anterior vitrectomy can effectively resolve aqueous misdirection, the macular retinoschisis may get worse. Awareness of this risk may aid in surgical planning and postoperative management in these patients.
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