Long noncoding RNAs are widely acknowledged as a group of regulatory factors in various diseases, especially in cancers. KCNQ1 overlapping transcript 1 (KCNQ1OT1) has been reported as oncogene in human cancers. However, the role of KCNQ1OT1 in colorectal cancer (CRC) has not been fully explained. Based on the database analysis, KCNQ1OT1 was highly expressed in CRC samples and predicted the poor prognosis for CRC patients. Functional experiments revealed that KCNQ1OT1 knockdown negatively affected the proliferation, migration and epithelial-mesenchymal transition (EMT) in CRC cells. Moreover, we identified the cytoplasmic localization of KCNQ1OT1 in CRC cells, indicating the posttranscriptional regulation of KCNQ1OT1 on gene expression. Mechanism experiments including RNA Immunoprecipitation (RIP) assay and dual luciferase reporter assays verified that KCNQ1OT1 acted as a competing endogenous RNA (ceRNA) in CRC by sponging microRNA-217 (miR-217) to up-regulate the expression of zinc finger E-box binding homeobox 1 (ZEB1). Further mechanism investigation revealed that ZEB1 enhanced the transcription activity of KCNQ1OT1 by acting as a transcription activator. Finally, rescue assays were designed to demonstrate the effect of KCNQ1OT1-miR-217-ZEB1 feedback loop on proliferation, migration, and EMT of CRC cells. In brief, our research findings revealed that ZEB1-induced upregulation of KCNQ1OT1 improved the proliferation, migration and EMT formation of CRC cells via regulation of miR-217/ZEB1 axis.
In recent years, the incidence of colorectal cancer (CRC) has increased and research into new treatment methods for CRC has become a hot topic. Naringin has an inhibitory effect on the PI3k/AKT/mTOR signaling pathway in various tumor cell types and the effect of naringin is closely related to the occurrence and proliferation of tumor cells. The aim of this present study was to investigate whether naringin could inhibit the proliferation of CRC cells by inhibiting the PI3K/AKT/mTOR signaling pathway. This could provide a more mechanism-based treatment for CRC. MTT assays were used to detect the proliferation of CRC cells treated with various concentrations of naringin. The degree of apoptosis and the expression of apoptosis-related proteins (Bcl-2 and Bax) in CRC cells stimulated by naringin was detected using flow cytometry and western blot assays, respectively. The expression levels of PI3K/AKT/mTOR-related proteins [PI3K, AKT, mTOR, phosphorylated (p)-PI3K, p-AKT and p-mTOR] after naringin stimulation in CRC cells were detected using western blot assays. Naringin inhibited the proliferation of CRC cells in a dose-dependent manner. Naringin promoted the apoptosis of CRC cells and inhibited the activation of the PI3K/AKT/mTOR signaling pathway in a dose-dependent manner. The results demonstrated that naringin may be a promising therapeutic agent for the treatment of CRC, which may inhibit the proliferation of CRC cells and induce apoptosis by inhibiting the PI3K/AKT/mTOR signaling pathway.
Colon cancer is a common and deadly human digestive tract malignant tumor with poor prognosis. Immunotherapy has elicited tremendous success as a treatment modality for multiple solid tumors. Triptolide is extracted from the traditional Chinese medicine Tripterygium wilfordii Hook. F which shows various pharmacological actions including antitumor, anti-inflammatory, antimicrobial, antifibrosis, and antirheumatic. However, the influence of triptolide treatment on remodeling tumor immune microenvironment is still unknown in colon cancer. This study was aimed to investigate the therapeutic effect of triptolide treatment on colon cancer and the impact on tumor immune microenvironment and its underlying mechanism. We used CT26 subcutaneous tumors to conduct in vivo experiments and HT29, CT16, and Raw264.7 cells to perform in vitro assays. Triptolide had a therapeutic effect against colon cancer in vivo. Triptolide treatment distinctly inhibited the proliferation of colon cancer cells and induced apoptosis in vitro. In colon cancer immune microenvironment, triptolide treatment decreased the infiltration of tumor-associated macrophages through downregulating tumor-derived CXCL12 expression via nuclear factor kappa B and extracellular signal-regulated protein kinases 1 and 2 axis to remodel the immune microenvironment. Triptolide-educated colon cancers retarded the macrophages polarize to anti-inflammatory M2 status by decreasing the expression of Arg-1, CD206, and interleukin-10. Moreover, triptolide inhibited the migration of colon cancer cells via decreasing vascular endothelial growth factor expression. Our results identified the role of triptolide treatment in remodeling colon cancer immune microenvironment along with the distinct cytotoxicity function against colon cancer cells, which may provide the evidence for triptolide treatment in clinical.
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