Overexpression of FOXM1 predicts poor prognosis and promotes cancer cell proliferation, migration and invasion in epithelial ovarian cancer

Wen, Ning; Wang, Yu; Li, Wen; Zhao, Shuhua; Ai, Zhen-Hua; Wang, Yi; Wu, Bo; Lu, Huai-Xiu; Yang, Hong; Li, Wenchao; Yu, Li

doi:10.1186/1479-5876-12-134

Cited by 84 publications

(69 citation statements)

References 28 publications

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“…Previously, FOXM1 has been reported to promote the expression of many factors that are involved in the degradation of extra cellular matrix and angiogenesis such as uPAR, MMP-2, MMP-9, and vascular endothelial growth factor A (VEGF-A) [16,17]. Thus, qRT-PCR and Western blotting assays were performed to detect the effects of miR-149 or FOXM1 expression on the mRNA and protein expression of MMP-2, MMP-9, VEGF-A and uPAR in CRC cells.…”

Section: Resultsmentioning

confidence: 99%

MicroRNA-149 Suppresses Colorectal Cancer Cell Migration and Invasion by Directly Targeting Forkhead Box Transcription Factor FOXM1

Liu

Mao

et al. 2015

Cell Physiol Biochem

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Background/Aims: The aim of this study is to investigate the clinicopathological and prognostic values of miR-149 expression and its roles in colorectal cancer (CRC) progression. Methods: qRT-PCR was performed to detect miR-149 expression in CRC cell lines or tissues. Also, the clinical significance of miR-149 expression was investigated. The study further explored whether miR-149 inhibits migration and invasion of CRC cells by targeting the mammalian Forkhead Box M1 (FOXM1). Results: miR-149 was significantly downregulated in CRC tissues, and low miR-149 expression was observed to be significantly correlated with lymph node or distant metastasis and advanced TNM stage of CRC patients. Patients with low miR-149 expression showed poorer prognosis than those with high miR-149 expression, and multivariate analyses indicated that status of miR-149 expression might be an independent prognostic factor. Gain- and loss - of - function assays indicated that miR-149 significantly inhibited growth, migration and invasion of CRC cells by targeting FOXM1. Furthermore, FOXM1 was significantly uiregulated in CRC tissues and inversely correlated with miR-149 expression. Conclusions: mR-149 was an independent prognostic factor and could inhibit migration and invasion of CRC cells, at least partially by targeting FOXM1.

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Section: Resultsmentioning

confidence: 99%

MicroRNA-149 Suppresses Colorectal Cancer Cell Migration and Invasion by Directly Targeting Forkhead Box Transcription Factor FOXM1

Liu

Mao

et al. 2015

Cell Physiol Biochem

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“…MMP-2 and MMP-9 principally function in tumor invasion and migration (49), whereas VEGF is a key factor in angiogenesis (50,51). In epithelial ovarian cancer cells, FOXM1 downregulation led to reduced expression of MMP-2, MMP-9 and VEGF (52). In a previous study, the present authors used RNAi to inhibit the expression of FOXM1 in cervical cancer cells, which consequently suppressed the activity and expression of MMP-2, MMP-9 and VEGF (18).…”

Section: A B C D E F G Hmentioning

confidence: 86%

Association between FOXM1 and hedgehog signaling pathway in human cervical carcinoma by tissue microarray analysis

et al. 2016

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Abstract. Forkhead box M1 (FOXM1) and hedgehog (Hh) signaling pathway are implicated in the formation and development of human tumors, including cervical cancer. Previous studies have indicated that FOXM1 may be a downstream target gene of the Hh signaling pathway, but their association in cervical cancer is largely unknown. In the present study, the expression of FOXM1 and Hh signaling molecules was evaluated by immunohistochemical analysis in a tissue microarray that contained 70 cervical cancer tissues and 10 normal cervical tissues. In addition, the association of these molecules with clinicopathological parameters, and the association between FOXM1 and various molecules involved in the Hh signaling pathway was investigated. The results indicated that FOXM1 and Hh signaling molecules were overexpressed in cervical cancer tissues. The protein expression levels of FOXM1, glioma-associated oncogene 1 (GLI1) and smoothened (SMO) correlated with the clinical stage of the tumors, while the protein expression levels of Sonic Hh (SHh), patched 1 (PTCH1) and GLI1 correlated with the pathological grade of the tumors. The expression levels of GLI1 were lower in tissues without lymph node metastasis than in tissues with lymph node metastasis. In addition, FOXM1 expression correlated with GLI1, SHh and PTCH1 expression in cancer tissues. These findings confirmed the participation of FOXM1 and the Hh signaling pathway in cervical cancer. Furthermore, the finding that FOXM1 may be a downstream target gene of the Hh signaling pathway in cervical cancer provides a potential novel diagnostic and therapeutic target for cervical cancer.

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“…Interestingly, the effect exerted by miR-194 on FoxM1 was suggested to be involved in the EMT process of neoplasms [21], and several microarray assays revealed that FoxM1 was highly expressed within > 20 solid neoplasms, including hepatocellular carcinoma, pancreatic adenocarcinoma, mastocarcinoma, ovarian cancer, lung cancer and CRC [43][44][45][46][47]. Besides, FoxM1 was over-expressed within actively-proliferating tumor cells, and it functioned to facilitate cell multiplication mainly by regulating cell cycle-specific genes [48].…”

Section: Discussionmentioning

confidence: 99%

The Effect of LncRNA H19/miR-194-5p Axis on the Epithelial-Mesenchymal Transition of Colorectal Adenocarcinoma

Chang-feng

Wang³

et al. 2018

Cell Physiol Biochem

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Background/Aims: Since the combined actions of lncRNAs and miRNAs have been considered to be involved in the occurrence and development of various neoplasms, the main purpose of this study was to discover whether and how lncRNA H19 and miR-194 influenced the epithelial-mesenchymal transition (EMT) process of colorectal adenocarcinoma (CRA). Methods: Totally 214 pairs of CRA and adjacent normal tissues were collected, and 5 human CRA cell lines (i.e. HCT116, HT-29, RKO SW280 and Lovo) were purchased. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was adopted to quantify the H19 and miR-194-5p expressions in cells and tissues. The expressions of FoxM1, E-cadherin, vimentin, N-cadherin were determined using western blot. On the side, si-H19, si-NC, miR-194-5p mimic, miR-194-5p inhibitor and negative control (NC) were transfected into CRA cell lines. Meanwhile, the invasive, migratory and proliferative conditions of the cells were assessed through transwell, wound healing and colony-forming experiments, with final verification of the relationship between H19 and miR-194-5p employing dual-luciferase reporter gene assay. Results: Highly-expressed H19, lowly-expressed miR-194-5p, low-grade differentiation and lymph node metastasis appeared as the independent predictors of unfavorable prognosis in CRA patients’ (all P< 0.05). It indicated that FoxM1 expression displayed positive correlations with H19 expression, yet negative associations with miR-194-5p expression within CRA tissues (P< 0.05). In addition, transfection of H19-siRNA and miR-145-5p mimic triggered a conspicuous increase in E-cadherin expression, as well as an evidently down-regulation in vimentin and N-cadherin expressions within HT29 and RKO cells (P< 0.05). On the other hand, the invasive and migratory capacities of CRA cells were significantly hindered (P< 0.05). Moreover, the luciferase reporter gene assay confirmed that H19 modified miR-194-5p expression through directly targeting at it (P< 0.05). Ultimately, FoxM1 could reverse the role of miR-194-5p in inhibiting invasion, migration and EMT of CRA cells (P< 0.05). Conclusion: LncRNA H19/miR-194/FoxM1 axis could serve as a profound target for the diagnosis and treatment of CRA.

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Overexpression of FOXM1 predicts poor prognosis and promotes cancer cell proliferation, migration and invasion in epithelial ovarian cancer

Cited by 84 publications

References 28 publications

MicroRNA-149 Suppresses Colorectal Cancer Cell Migration and Invasion by Directly Targeting Forkhead Box Transcription Factor FOXM1

MicroRNA-149 Suppresses Colorectal Cancer Cell Migration and Invasion by Directly Targeting Forkhead Box Transcription Factor FOXM1

Association between FOXM1 and hedgehog signaling pathway in human cervical carcinoma by tissue microarray analysis

The Effect of LncRNA H19/miR-194-5p Axis on the Epithelial-Mesenchymal Transition of Colorectal Adenocarcinoma

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