lncRNA IUR upregulates miR-34a to inhibit pancreatic adenocarcinoma cell migratory and invasive abilities

Oncol Lett. 2021 Jul;22(1):567. doi: 10.3892/ol.2021.12828. Epub 2021 May 29.

Abstract

The long non-coding RNA (lncRNA) imatinib-upregulated (IUR) has been recently reported as a tumor suppressor in leukemia. Preliminary microarray data revealed a downregulation of IUR in pancreatic adenocarcinoma (PAAD) and a positive correlation with microRNA-34a (miR-34a) expression. The present study aimed to investigate the role of IUR in PAAD. This study included samples from 58 patients with PAAD and the PAAD cell lines Capan-2 and HPAC. Reverse transcription quantitative PCR was performed to determine gene expression levels. Cell transfections were carried out to assess gene interactions between IUR, miR-34a and CD44. Transwell assays were performed to explore the effects of transfections on cell invasive and migratory abilities. The results demonstrated that IUR was downregulated in PAAD tissue compared with adjacent non-tumor tissue samples and that low expression levels of IUR correlated with poor survival in patients with PAAD. In PAAD tissue samples, the expression of IUR positively correlated with miR-34a expression but negatively correlated with CD44 expression, which is a target of miR-34a. In PAAD cells, overexpression of IUR resulted in miR-34a upregulation and CD44 downregulation. miR-34a overexpression did not affect the expression of IUR but downregulated CD44. In PAAD cells, overexpression of IUR and miR-34a led to decreased invasive and migratory abilities. However, CD44 overexpression played an opposite role and attenuated the effects of IUR and miR-34a overexpression. In conclusion, the results from this study demonstrated that IUR may upregulate miR-34a expression in order to inhibit PAAD cell migration and invasion by downregulating CD44.

Keywords: CD44; imatinib-upregulated; long non-coding RNA; microRNA-34a; pancreatic adenocarcinoma.

Grants and funding

The present study was supported by The Science and Technology Program of Shaanxi Province of China (grant no. 2014K11-03-03-07) and The Natural Science Foundation of Shaanxi Province of China (grant no. 2016JM8093). The funding bodies had no role in the design of the study; collection, analysis and interpretation of data and writing of the manuscript.