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.

journal_name

Cell Death Dis

journal_title

Cell death & disease

authors

Huang Z,Li Q,Luo K,Zhang Q,Geng J,Zhou X,Xu Y,Qian M,Zhang JA,Ji L,Wu J

doi

10.1038/s41419-019-1604-3

subject

Has Abstract

pub_date

2019-05-08 00:00:00

pages

372

issue

5

issn

2041-4889

pii

10.1038/s41419-019-1604-3

journal_volume

10

pub_type

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