Oncology reports
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Tripartite motif-containing 59 (TRIM59) belongs to the tripartite motif (TRIM) protein family and is upregulated in various malignancies. However, its expression in colorectal cancer (CRC) is still unknown. In the present study, we examined the expression and biological function of TRIM59 in CRC. ⋯ Further investigation revealed that knockdown of TRIM59 effectively reversed the expression of epithelial-mesenchymal transformation‑related proteins vimentin, Snail and E-cadherin. Our preliminary results confirm that TRIM59 can be mediated by PI3K/AKT signaling. TRIM59 functions as an oncogene in CRC progression, which could be a novel target for the detection and treatment of CRC.
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Epithelial-mesenchymal transition (EMT) plays a critical role in the process of cancer invasion and metastasis. The Wnt/β-catenin signaling pathway is known as a stimulative factor, which may trigger EMT and metastasis of cancer cells. In addition, several microRNAs (miRNAs) have been proven to regulate the EMT process. ⋯ Wnt10b, a promoting molecule of the Wnt/β-catenin signaling pathway, was demonstrated by dual‑luciferase reporter assay to be a direct target of miR‑148a. Subsequently, we found that miR‑148a negatively regulated the protein expression of β-catenin, cyclin D1 and MMP-9, which were important components of the Wnt/β-catenin signaling pathway. In conclusion, these findings revealed that miR-148a suppresses EMT and invasion of pancreatic cancer cells by targeting Wnt10b and inhibiting the Wnt/β-catenin signaling pathway, and thus, miR-148a may serve as a novel therapeutic target for pancreatic cancer.
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Lung cancer is one of the most lethal malignancies worldwide. To reduce the high morbidity and mortality of the disease, sensitive and specific biomarkers for early detection are urgently needed. Tumor-specific microRNAs (miRNAs) seem to be potential biomarkers for the early diagnosis and treatment of cancer. ⋯ In addition, upregulation of miR-205-5p, miR-3917 and downregulation of miR-30a-3p, miR-30a-5p, miR-30c-2-3p, miR-30d-5p, miR-27a-5p increased the risk of lung cancer by conditional logistic regression analysis. The diagnostic accuracy of miR-205-5p, miR-3917, miR-27a-5p, miR-30a-3p, miR-30a-5p, miR-30c-2-3p, miR-30d-5p showed that their corresponding AUCs were 0.728, 0.661, 0.637, 0.758, 0.772, 0.734, 0.776, respectively. Therefore, there are a set of signature miRNAs which may be promising biomarkers for the early screening of high-risk populations and early diagnosis of lung cancer.
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Epigenetics is a discipline that studies heritable changes in gene expression that do not involve altering the DNA sequence. Over the past decade, researchers have shown that epigenetic regulation plays a momentous role in cell growth, differentiation, autoimmune diseases, and cancer. The main epigenetic mechanisms include the well-understood phenomenon of DNA methylation, histone modifications, and regulation by non-coding RNAs, a mode of regulation that has only been identified relatively recently and is an area of intensive ongoing investigation. ⋯ However, taken together, a wide variety of recent studies have suggested that miRNAs, piRNAs, endogenous siRNAs, and long non-coding RNAs are the most common regulatory RNAs, and, significantly, there is a growing body of evidence that regulatory non-coding RNAs play an important role in epigenetic control. Therefore, these non-coding RNAs (ncRNAs) highlight the prominent role of RNA in the regulation of gene expression. Herein, we summarize recent research developments with the purpose of coming to a better understanding of non-coding RNAs and their mechanisms of action in cells, thus gaining a preliminary understanding that non-coding RNAs feed back into an epigenetic regulatory network.
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Trifluridine/tipiracil (TFTD) is a combination drug that is used for the treatment of metastatic colorectal cancer and was formerly known as TAS-102. It is a combination of two active pharmaceutical compounds, trifluridine, an antineoplastic thymidine-based nucleoside analog, and tipiracil, which enhances the bioavailability of trifluridine in vivo. TFTD is used for the treatment of patients with unresectable advanced or recurrent colorectal cancer that is resistant to standard therapies. ⋯ The concentration of trifluridine incorporated into DNA in the HT-29 and HCT116 tumors was determined by liquid chromatography-tandem mass spectrometry. The incorporation levels following treatment with TFTD and nintedanib for 14 consecutive days were higher than those associated with TFTD treatment alone. The preclinical findings indicate that the combination therapy with TFTD and nintedanib is a promising treatment option for colorectal cancer.