<p>MiR-140 Resensitizes Cisplatin-Resistant NSCLC Cells to Cisplatin Treatment Through the SIRT1/ROS/JNK Pathway</p>

Abstract

Background: Although cisplatin is an effective chemotherapeutic drug that is commonly used for non-small-cell lung cancer (NSCLC) treatment, the drug resistance usually occurs during the long-term use of it. It is urgent to develop strategies to reduce the resistance of NSCLC cells to cisplatin. Methods: Cisplatin-resistant NSCLC cell lines (PC9/R and A549/R) were acquired through long-term exposure of PC9 and A549 cells to cisplatin. QRT-PCR analysis was performed to compare the expression of miR-140 between routine NSCLC cells and cisplatin-resistant NSCLC cells. CCK-8 assay was used to evaluate the effect of miR-140 on the sensitivity of PC9/R and A549/R to cisplatin. Western blot assay and luciferase reporter assay were used to confirm the regulation of miR-140 on SIRT1. Western blot and flow cytometry analysis were performed to evaluate the effect of miR-140 on the apoptosis pathway induced by cisplatin. Results: PC9/R and A549/R exhibited obviously lower sensitivity compared to their parental PC9 and A549 cells, respectively. Furthermore, PC9/R and A549/R cells expressed significantly lower levels of miR-140 compared to their parental PC9 and A549 cells, respectively. However, transfection with miR-140 mimics significantly resensitized the PC9/R and A549/R to cisplatin-induced cytotoxicity. In the mechanism research, we confirmed that SIRT1 was overexpressed and was targeted by miR-140 in PC9/R and A549/R. Furthermore, overexpression of SIRT1 was responsible for the resistance to cisplatin in PC9/ R and A549/R cells. Transfection with miR-140 was able to inhibit the expression of SIRT1 and thus inhibited the SIRT1/ROS/JNK pathway. As a result, the PC9/R and A549/R cells restored the sensitivity to cisplatin-induced apoptosis. Conclusion: MiR-140 resensitizes cisplatin-resistant NSCLC cells to cisplatin treatment through the SIRT1/ROS/JNK pathway.

[Retracted] Circ TYMP1 Inhibits Carcinogenesis and Cisplatin Resistance in Ovarian Cancer by Reducing Smad2/3 Phosphorylation via a MicroRNA‐182A‐3p/TGF1B Axis

“…Cisplatin can perform its apoptosis-related activity in cancer cells via modifying ovarian carcinoma and increasing the formation of reactive oxygen species (ROS) [3]. Oncogenic cells have a Contrast Media & Molecular Imaging greater capacity to respond to the anticancer drug cisplatin when Smad2/3 is activated [21]. e activation of Smad2/3 results in an increase in the synthesis of apoptosis-related proteins and a reduction in the activity of antiapoptotic proteins.…”

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

“…In increasing CP sensitivity, miRNA-140 down-regulates SIRT1 expression to promote ROS levels. Then, ROS induces JNK phosphorylation to increase CP-mediated apoptosis [113]. As more experiments are performed, different molecular pathways are revealed that mediate CP resistance of thoracic cancers.…”

MiR-140 leads to MRE11 downregulation and ameliorates oxaliplatin treatment and therapy response in colorectal cancer patients

“…They published evidence that overexpression of miR-29b re-sensitized OR-SW480 cells to oxaliplatin treatment. MiR-140 also re-sensitizes cisplatin-resistant NSCLC cells to cisplatin treatment through the SIRT1/ROS/JNK pathway ( 29 ).…”