FOXD1 is targeted by miR-30a-5p and miR-200a-5p and suppresses the proliferation of human ovarian carcinoma cells by promoting p21 expression in a p53-independent manner

Abstract

High-grade serous ovarian carcinoma (HGSOC) accounts for the highest number of deaths among patients with epithelial ovarian cancer. However, the molecular mechanisms underlying HGSOC tumorigenesis are currently unclear. In the present study, a lentiviral expression system was employed to manipulate forkhead box D1 (FOXD1) expression in ovarian cancer cells. Immunohistochemical staining was used to examine the expression of FOXD1 in tissue samples. Clonogenic and MTT assays were employed to evaluate cell proliferation, and flow cytometry was applied for cell cycle analysis. Dual-luciferase reporter and chromatin immunoprecipitation assays were used to determine the role of FOXD1 in regulating p21 expression. The results demonstrated that FOXD1 expression was downregulated in HGSOC, and high expression levels of FOXD1 were found to be a predictor of good prognosis. FOXD1 significantly inhibited the proliferation of human ovarian cancer cells and induced cell cycle arrest at G1 phase in vitro. In addition, exogenous FOXD1 expression inhibited ovarian cancer cell growth in vivo. Furthermore, microRNA (miR)-30a-5p and miR-200a-5p were observed to be upregulated in HGSOC, and function as direct negative regulators of FOXD1 by targeting its 3'-untranslated region. The present study also revealed that FOXD1 promotes p21 expression in a p53-independent manner. In conclusion, the results of the present study indicate a direct association between FOXD1 and p21 that may be mediated by miR-30a-5p and miR-200a-5p. The authors hypothesize that FOXD1 may serve as a biomarker or therapeutic target in HGSOC.

Circulating microRNA/isomiRs as novel biomarkers of esophageal squamous cell carcinoma

“…According to previous reports, miR-30a-5p plays a dual role in different types of cancer as either an oncogene or onco-suppressor [28]. Function of miR-30a-5p as cancer activators has been reported in pharyngeal cancer [29], ovarian cancer [30] and glioma [31]. Their expression profiles also differ between cancer and normal tissue.…”

MicroRNA‐200a suppresses prostate cancer progression through BRD4/AR signaling pathway

“…Oncogenic factors, such as miR‐203, miR‐410, and miR‐34a, have been identified as carcinogenic factors that promote proliferation of PCa cells . Notably, miR‐200a, a member of the miR‐200 family, has been shown to participate in several biological processes that regulate the progression of tumors . However, the role of miR‐200a in prostate cancer development and progression has not been investigated.…”

miR‐30a inhibits androgen‐independent growth of prostate cancer via targeting MYBL2, FOXD1, and SOX4

“…MYBL2 previously had been reported as miR‐30a target in acute myeloid leukemia 42 and non–small‐cell lung cancer 43 . FOXD1 was also a miR‐30a target in human ovarian carcinoma 44 and osteosarcoma 45 . However, it has not yet been established whether miR‐30a directly targets MYBL2 and FOXD1 to affect AI growth in PCa.…”