miR-340-FHL2 axis inhibits cell growth and metastasis in ovarian cancer

Abstract

Although increasing evidence indicated that deregulation of microRNAs (miRNAs) contributed to tumor initiation and progression, but little is known about the biological role of miR-340 in ovarian cancer (OC). In this study, we found that miR-340 expression was downregulated in OC tissues compared with its expression in normal ovarian epithelium and endometrium, and treatment with 5-aza-2′-deoxycytidine (5-Aza-dC) or trichostatin A (TSA) increased miR-340 expression in OC cells. In addition, ectopic miR-340 expression inhibited OC cell growth and metastasis in vitro and in vivo. Four and a half LIM domains protein 2 (FHL2) was confirmed as a direct target of miR-340 and silencing FHL2 mimicked the effects of miR-340 in OC cells. Further mechanistic study showed that miR-340 inhibited the Wnt/β-catenin pathway by targeting FHL2, as well as downstream cell cycle and epithelial-to-mesenchymal transition (EMT) signals in OC cells. Moreover, the greatest association between miR-340 and FHL2 was found in 481 ovarian serous cystadenocarcinoma tissues via pan-cancer analysis. Finally, we revealed that lower miR-340 or higher FHL2 was associated with poor OC patient outcomes. Our findings indicate that the miR-340-FHL2 axis regulates Wnt/β-catenin signaling and is involved in tumorigenesis in OC. Therefore, manipulating the expression of miR-340 or its target genes is a potential strategy in OC therapy.

The Function of LINC00662/miR-340-5p/STAT3 Regulation Loop in Promoting Tumorigenesis and Development of Glioma

“…Our evidences indicated that miR-340-5p acts as a tumor suppressor in glioma. Those data were in accordance with the previous reports that miR-340 functioned as a tumor suppressor in several cancers, including gastric cancer, breast cancer, squamous cell carcinoma, ovarian cancer, osteosarcoma, multiple myeloma and non-small cell lung cancer [44,45]. In this study, we found that the expressions of LINC00662, STAT3 and STAT3 target genes were downregulated with miR-340-5p OE in U251 cells.…”

Long non-coding RNA TUG1 promotes cell progression in hepatocellular carcinoma via regulating miR-216b-5p/DLX2 axis

“…Cell cycle and apoptosis assays were carried out as described previously [20]. The transfected cells were collected and washed twice at 4 °C with PBS, followed by fixation using cold 70% ethanol at 4 °C overnight.…”

miR‐5188 augments glioma growth, migration and invasion through an SP1‐modulated FOXO1‐PI3K/AKT‐c‐JUN‐positive feedback circuit

“…The staining intensity was scored as described previously. 10 The score lower than or equal to 6 indicated low expression, while the score higher than 6 indicated high expression.…”

“…Accumulating reports have supported that microRNAs (miR-NAs) participated in numerous processes, including development, proliferation, cell cycle control and cellular differentiation, and are involved in regulating many human cancers. [5][6][7][8][9][10][11] miRNAs may serve as tumour suppressors or oncogenes depending on the cancer type.…”