miR-485-5p inhibits bladder cancer metastasis by targeting HMGA2

Abstract

MicroRNA (miRNA or miR)‑485 is a functional miRNA which has received much attention in recent years. However, little is known about the expression of miR‑485 or the role it plays in bladder cancer [namely in metastasis and epithelial‑mesenchymal transition (EMT)]. Thus, in the present study, we aimed to detect the expression of miR‑485 in human bladder cancer tissues and bladder cancer cell lines, and to examine the effects of miR‑485‑5p on bladder cancer cell metastasis and EMT. We found that the expression of miR‑485‑5p was downregulated in the human bladder cancer tissues and different bladder cancer cell lines compared with the normal tissues and cell lines, as demonstrated by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). We enforced the expression of miR‑485‑5p in T24 cells and inhibited the expression of miR‑485‑5p in SW780 cells by transfection with miR‑485‑5p mimic or miR‑485‑5p inhibitor, respectively. The ectopic expression of miR‑485‑5p was shown to inhibit cell metastasis and EMT, whereas the inhibition of miR‑485‑5p expression promoted cell metastasis and EMT, as shown by transwell‑matrigel assay, cell adhesion assay and western blot analysis. Furthermore, a luciferase reporter assay revealed that high mobility group AT‑hook 2 (HMGA2) was a direct target of miR‑485‑5p and that the overexpression of HMGA2 reversed the effects of miR‑485‑5p on cell metastasis and EMT. In conclusion and to the very best of our knowledge, the present study, for the first time, identified miR‑485‑5p as a suppressive miRNA in human bladder cancer, and demonstrated that miR‑485‑5p inhibits cell metastasis and EMT at least partly through the suppression of HMGA2 expression.

Deregulated MicroRNAs in Cancer-Associated Fibroblasts from Front Tumor Tissues of Lung Adenocarcinoma as Potential Predictors of Tumor Promotion

“…As reported previously, miR-145-3p and miR-505-3p (Yamamoto et al 2011;Matsushita et al 2016) as well as miR-410-3p and miR-485-5p (Shiah et al 2014;Chen et al 2015;Mussnich et al 2015) are downregulated in tumor tissues from different cancers and appear to function as tumor suppressor genes. Consistent with these reports, the pathway enrichment analysis in this study showed that miR-145-3p, miR-299-3p (F-CAFs vs. NFs) and miR-410-3p (F-CAFs vs. In-CAFs) were significantly associated with "pathways in cancer", whereas miR-505-3p (F-CAFs p value of ≤ 0.05 was used to select significant pathways.…”

“…Next, we selected ten different candidate miRNAs for RT-qPCR validation of the microarray results using matched F-CAFs, In-CAFs and NFs (triplets) from twelve patients diagnosed with primary lung adenocarcinoma. We chose these candidate miRNAs from the microarray results because these miRNAs exhibited the largest fold change or/ and were associated with previously published evidence of relationships with tumors (Yamamoto et al 2011;Shiah et al 2014;Chen et al 2015;Guo et al 2015a;Guo et al 2015b;Mussnich et al 2015;He et al 2016;Matsushita et al 2016). The selected candidate miRNAs were miR- 145-3p, miR-299-3p, and miR-505-5p (downregulated in F-CAFs vs. NFs); miR-6875-3p and miR-6735-5p (upregulated in F-CAFs vs. NFs); miR-181c-5p, miR-5006-5p, and miR-6867-5p (downregulated in In-CAFs vs. NFs); miR-410-3p and miR-485-5p (downregulated in F-CAFs vs. In-CAFs); and miR-6875-3p and miR-6735-5p (upregulated in F-CAFs vs. In-CAFs) ( Table 1).…”

The transcriptional modulator HMGA2 promotes stemness and tumorigenicity in glioblastoma

“…In contrast, we find increased HMGA2 by immunohistochemistry and western blot in 70 percent of GBM, suggesting that multiple factors may regulate HMGA2. In other tumor types, HMGA2 levels are controlled by Transforming Growth Factor-β (TGF-β) [34], Raf-1 kinase inhibitory protein [66-68], RUNX1 [37], and several microRNAs [35, 39, 69-73]. …”

Long Non-Coding RNAs: Key Regulators of Epithelial-Mesenchymal Transition, Tumour Drug Resistance and Cancer Stem Cells

“…It achieves this by acting as a ceRNA for miR-145, which (a) directly inhibits ZEB2; and (b) indirectly inhibits ZEB1 via targeting Oct4, a transcriptional activator of ZEB1 [185]. UCA1 has also been shown to suppress metastasis of epithelial ovarian cancer by functioning as a ceRNA for miR-485-5p [188], a miRNA which blocks EMT and metastasis through its targeting of MMP14 and HMGA2 [188,300]. UCA1 has also been shown to regulate EMT in Gastric Cancer as, silencing of UCA1 resulted in decreased levels of vimentin and snail, with concomitant elevated levels of E-cadherin [196].…”