Long noncoding RNA (lnc RNA ) DLEU 2 has been shown to be dysregulated in several type of tumor. However, the potential biological roles and molecular mechanisms of DLEU 2 in pancreatic cancer ( PC ) progression are poorly understood. In this study, we found that the DLEU 2 level was substantially upregulated in PC tissues and PC cell lines, and significantly associated with poor clinical outcomes in PC patients. Overexpression of DLEU 2 significantly induced PC cell proliferation and invasion, whereas knockdown of DLEU 2 impaired cell proliferation and invasion in vitro. Furthermore, bioinformatics analysis, luciferase reporter assay, and RNA immunoprecipitation assay revealed that DLEU 2 directly bond to microRNA‐455 (miR‐455) and functioned as an endogenous sponge for miR‐455, which could remarkably suppress cell growth and invasion. We also determined that SMAD 2 was a direct target of miR‐455, and the restoration of SMAD 2 rescued cell growth and invasion that were reduced by DLEU 2 knockdown or miR‐455 overexpression. In addition, low miR‐455 expression and high SMAD 2 expression was correlated with poor patient survival. These results indicate that DLEU 2 is an important promoter of PC development, and targeting the DLEU 2/miR‐455/ SMAD 2 pathway could be a promising therapeutic approach in the treatment of PC .

Background: microRNAs (miRNAs) are emerging as critical regulators of multidrug resistance (MDR) in gastric cancer, a major cause of chemotherapy failure. miR-625 is downregulated in gastric cancer and negatively associated with metastasis. In the current study, we aimed to investigate whether miR-625 regulates MDR in gastric cancer. Methods: The level of miR-625 in gastric cancer cells with or without MDR was quantified by quantitative reverse transcription PCR (qRT-PCR) analysis. The sensitivity of gastric cancer cells to chemotherapeutic agents was assessed by MTT assay. The protein expression was determined by Western blot analysis, and the luciferase reporter assay was applied to confirm miR-625 regulation of the potential target. Results: miR-625 is downregulated in MDR gastric cancer cells compared with chemosensitive counterparts. In addition, miR-625 increases the sensitivity and promotes apoptosis of gastric cancer cells when treated with different chemotherapeutic agents. Moreover, miR-625 directly targets the aldehyde dehydrogenase 1A1 (ALDH1A1), and importantly, the restoration of ALDH1A1 expression rescues miR-625 effects on MDR in gastric cancer cells. Conclusion: miR-625 reverses MDR in gastric cancer cells by targeting ALDH1A1. Hence, our study identifies miR-625 as a novel regulator of MDR in gastric cancer cells, and implicates its potential application for overcoming MDR in gastric cancer chemotherapy.

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