Long noncoding RNA DIO3OS interacts with miR-122 to promote proliferation and invasion of pancreatic cancer cells through upregulating ALDOA

Abstract

Background Long noncoding RNA (lncRNA) has been implicated in numerous tumors, including pancreatic cancer (PC). However, the precise cellular roles and molecular mechanisms of lncRNA DIO3OS on PC development remains to be fully clarified. Methods We performed the meta-analysis on PC samples and non-tumor samples retrieved from the TCGA database, and measured the levels of DIO3OS in PC cell lines and a normal pancreatic duct epithelial cell line HPDE6-C7. Cell proliferation was evaluated via CCK-8 assay. Cell invasion in vitro was investigated by transwell assay. The RNA immunoprecipitation assay and luciferase reporter assay was utilized to confirm the putative miR-122-binding site in DIO3OS. The effects of DIO3OS on PC progression were tested using in vivo subcutaneous xenografts. Results Our results showed that DIO3OS was highly expressed in human PC tissues and PC cell lines. DIO3OS exhibited oncogenic properties in stimulating PC cell proliferation and invasion in vitro and promoting cancer growth in vivo. Through online predictive tools and functional experiments, we found that DIO3OS could bind directly to microRNA-122 (miR-122) and inhibited its expression, which functioned as a tumor suppressor in PC cells. We also verified that ALDOA was the direct target of miR-122, and the tumor suppressive effects caused by DIO3OS knockdown or miR-122 overexpression could be rescued by re-expression of ALDOA in PC cells. Conclusions Overall, our study suggested that lncRNA DIO3OS promotes PC cell growth and invasion by competing for miR-122 to modulate the expression of ALDOA. These findings yield a better understanding of the potential mechanisms by which gain of DIO3OS expression accelerates PC progression.

<p>Long Noncoding RNA DIO3OS Hinders Cell Malignant Behaviors of Hepatocellular Carcinoma Cells Through the microRNA-328/Hhip Axis</p>

“…By contrast, DIO3OS promoted cell proliferation and invasion through competing for miR-122 to upregulate ALDOA expression in pancreatic cancer. 24 A plethora of researches on miR-328 have paid much attention to its functions on cell growth, invasion and migration in cancers, including gastric cancer, 25 invasive breast cancer, 26 non-small cell lung cancer, 27 and most importantly, HCC. 28 Additionally, overexpression of metastasis associated in lung adenocarcinoma transcript-1 sequestered cytoplasmic miR-328-3p, culminating in insulin-like growth factor 1 receptor induction to mediate hypoxia-stimulated proliferation of pulmonary artery smooth muscle cells.…”

Bioinformatics analysis of LINC01554 and its co‑expressed genes in hepatocellular carcinoma

“…Based on a literature review, we chose DIO3OS, LINC01554, and LINC01093 for further investigation as they showed relevant biological functions. For example, previous studies have shown that DIO3OS is highly expressed in pancreatic cancer and DIO3OS was found to regulate pancreatic cancer cell proliferation and metastasis by affecting the miR-122/ALDOA axis (14). LINC01093 is a liver-specific lncRNA that was found to be significantly downregulated in HCC samples and could inhibit HCC cell growth and metastasis (15).…”

Glycometabolic rearrangements--aerobic glycolysis in pancreatic cancer: causes, characteristics and clinical applications

“…However, biochemical assays showed that methylene insertion weakened the effect of ND1 [ 140 ]. It is clear that the lncRNA DIO3OS promotes the growth of PDAC tumors with low expression of miR-122 and high expression of aldolase A [ 141 ]. Therefore, the DIO3OS/miR-122/aldolase A axis could be exploited as a therapeutic target in PDAC progression.…”