<p>Inhibition of TRIM32 Induced by miR-519d Increases the Sensitivity of Colorectal Cancer Cells to Cisplatin</p>

Abstract

Background: Colorectal cancer is a leading cause of cancer-related death in the world. Despite cisplatin is a commonly used chemotherapeutic drug for the colorectal cancer treatment, resistance of cancer cells to cisplatin restricts its clinical efficacy. It is important to explore the potential mechanisms and take strategies to sensitize colorectal cancer cells to cisplatin treatment. Methods: Differences of TRIM32 and miR-519d expression between colorectal cancer cells and human normal colon epithelial cells were evaluated by qRT-PCR and Western blot assays. Cytotoxicity of cisplatin against colorectal cancer cells was tested by CCK-8 assay. Generation of reactive oxygen species (ROS), mitochondrial membrane potential and apoptosis was measured by flow cytometry. Dual-luciferase reporter assay was used to validate the association between miR-519d and TRIM32. Results: Significant increase of TRIM32 expression in colorectal cancer tissues and cell lines was observed. TRIM32 negatively regulated the cisplatin sensitivity in colorectal cancer cells. Mechanically, overexpression of TRIM32 was induced by decrease of miR-519d. Exogenous miR-519d can inhibit the expression of TRIM32 and thus promoted the cisplatin-induced apoptosis through the mitochondrial pathway. Conclusion: Overexpression of TRIM32 was induced by the absence of miR-519d in colorectal cancer. MiR-519d can be used as a sensitizer during the cisplatin-based chemotherapy of colorectal cancer.

Elucidating Role of Reactive Oxygen Species (ROS) in Cisplatin Chemotherapy: A Focus on Molecular Pathways and Possible Therapeutic Strategies

“…Furthermore, miRNA-519d impedes CP resistance by inducing apoptosis through MCL-1-dependent mitochondrial pathway [93]. In colorectal cancer cells, miRNA-519d down-regulates the expression level of tripartite motif 32 (TRIM32) to enhance ROS levels, leading to mitochondrial dysfunction and increased CP sensitivity [94]. Investigating the expression level demonstrates that miRNAs with tumor-suppressing role undergo down-regulation in CP resistant-cancer cells.…”

Inhibition of TRIM32 by ibr‐7 treatment sensitizes pancreatic cancer cells to gemcitabine via mTOR/p70S6K pathway

“…It was reported that TRIM32 played a pro‐apoptotic role via destabilizing mitochondrial membrane potential and degradation of XIAP in normal cells 32,33 . In the context of cancer, TRIM32 was able to promote the proliferation and motility of lung, gastric, squamous cancer cells or contribute to cisplatin resistance in colorectal cancer, whereas the role of TRIM32 in PDAC cells remained unknown 34‐38 . In our study, we found that the combination treatment of ibr‐7 and gemcitabine could diminish TRIM32 at a transcriptional level, probably through enhancing the methylation status of TRIM32 (Figure 5F,G).…”

Inhibition of TRIM32 Attenuates the Apoptosis, Oxidative Stress and Inflammatory Injury of Podocytes Induced by High Glucose by Affecting the Akt/GSK-3β/Nrf2 Pathway

“…TRIM32 exerts a key role in regulating the survival and apoptosis of various cell types. TRIM32 can inhibit the apoptosis of cancer cells and enhances cell survival under exposure to chemotherapeutics [38][39][40].…”