FOXK1 interaction with FHL2 promotes proliferation, invasion and metastasis in colorectal cancer

Wu, Mingyan; Wang, J; Tang, Weimei; Zhan, Xiaozhi; Li, Y; Peng, Ying; Huang, Xiaoqing; Bai, Yang; Zhao, Jiajia; Li, A; Chen, C; Chen, Y; Peng, Hao; Ren, Yu; Li, G; Liu, S

doi:10.1038/oncsis.2016.68

Cited by 56 publications

(52 citation statements)

References 35 publications

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“…CCK-8 and Transwell assays, demonstrated that restoration of FOXK1 significantly abrogated the effects of LINC01503 knockdown on CRC cell proliferation and invasion, which suggested that FOXK1 has an oncogenic role in CRC. This result was consistent with that of a previous study on FOXK1 (25). Therefore, these results demonstrated that LINC01503 promotes CRC progression via enhancing the expression of FOXK1.…”

Section: Discussionsupporting

confidence: 93%

Long non‑coding RNA LINC01503 promotes colorectal cancer cell proliferation and invasion by regulating miR‑4492/FOXK1 signaling

et al. 2018

Exp Ther Med

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Increasing evidence indicates that long non-coding RNAs (lncRNAs) are closely associated with the progression of human cancer, including colorectal cancer (CRC). A previous study suggested that lncRNA LINC01503 promotes squamous cell carcinoma progression. However, the function of LINC01503 in CRC has remained elusive. The present study indicated that LINC01503 was significantly upregulated in CRC tissues compared with that in adjacent normal tissues as detected by reverse transcription-quantitative polymerase chain reaction. It was demonstrated that knockdown of long intergenic non-protein coding RNA (LINC)01503 markedly inhibited the proliferation and invasion of CRC cells, whereas overexpression of LINC01503 had the opposite effects, as indicated by Cell Counting kit-8 and Transwell assays. Mechanistically, it was revealed that LINC01503 serves as a sponge for microRNA (miR)-4492, which targets forkhead box K1 (FOXK1) in CRC cells. In addition, luciferase reporter assays demonstrated the direct binding of miR-4492 mimics to LINC01503 and to a sequence in the 3'-untranslated region of FOXK1. Furthermore, it was demonstrated that overexpression of LINC01503 reduced the availability of miR-4492 in CRC cells. Furthermore, miR-4492 mimics inhibited FOXK1 expression, while simultaneous overexpression of LINC01503 abolished this effect. Finally, it was demonstrated that restoration of FOXK1 abolished the inhibitory effect of LINC01503 knockdown on CRC cell proliferation and invasion. Taken together, the present results suggested that LINC01503 promotes CRC progression via acting as a competing endogenous RNA for miR-4492/FOXK1.

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Section: Discussionsupporting

confidence: 93%

Long non‑coding RNA LINC01503 promotes colorectal cancer cell proliferation and invasion by regulating miR‑4492/FOXK1 signaling

et al. 2018

Exp Ther Med

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“…Conversely, FOXK1 knockdown in Snail-overexpressing cells led to EMT reversion (Fig. 2B).Some reports have shown actin cytoskeleton regulation of the EMT in metastatic cancer cells [12,26]. Thus, we stained F-actin with phalloidin, followed by immunofluorescence analysis, which showed that Snail-overexpressing cells had an elongated cellular morphology and the presence of F-actin fibers compared with vector cells, a hallmark of the mesenchymal phenotype.…”

Section: Snail-foxk1 Axis Promotes Emt-mediated Crc Cells Invasion Anmentioning

confidence: 76%

“…FOXK1 is a proto-oncoprotein that is overexpressed in various cancer types [31][32][33]. Ectopic expression of FOXK1 markedly enhances cell proliferation, migration, and invasion in gastrointestinal cancer cells [15,26]. We recently demonstrated that FOXK1 induces EMT progression and predicts poor prognosis in human gastric cancer [15,34].…”

Section: Discussionmentioning

confidence: 99%

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Snail/FOXK1/Cyr61 Signaling Axis Regulates the Epithelial–Mesenchymal Transition and Metastasis in Colorectal Cancer

Huang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Metastasis is the primary cause of colorectal cancer (CRC)-related death. However, the molecular mechanisms underlying metastasis in CRC remain unclear. Methods: We evaluated mRNA and protein expression levels by quantitative real-time reverse transcription PCR, western blotting, immunofluorescence, tissue microarrays, and immunohistochemistry assays. We also assessed the migration and invasion abilities of CRC cells in vitro by wound healing assays, invasion and migration assays, western blot analysis, and immunofluorescence. Tumor metastasis was evaluated in nude mice in vivo. Results: A positive correlation was observed between the expression patterns of Forkhead box k1 (FOXK1) and Snail in CRC. Luciferase reporter and chromatin immunoprecipitation assays demonstrated that Snail directly bound to and activated the human FOXK1 gene promoter. Moreover, the Snail-FOXK1 axis promote epithelial mesenchymal transition (EMT)-mediated CRC cell invasion and metastasis. FOXK1 and Snail expression levels were correlated with tumor progression and served as significant predictors of overall survival in patients with CRC. Furthermore, overexpression of FOXK1 induced the EMT by upregulating the expression of cysteine-rich angiogenic inducer 61 (Cyr61). Luciferase assays showed that Cyr61 was a direct transcriptional target of FOXK1. Down regulation of Cyr61 decreased FOXK1-enhanced “CRC cell” migration, invasion, and metastasis. Additionally, FOXK1 expression was positively correlated with Cyr61 expression and was associated with poor prognosis. Conclusions: The Snail/FOXK1/Cyr61 signaling axis regulates the EMT and metastasis of CRC.

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“…As previous reports have demonstrated, FOXK1 promotes cell proliferation in prostate cancer (39), colorectal cancer (40) and gastric cancer (41). In order to investigate whether the enhancing effect of FOXK1 on cell proliferation is caused by inhibition of apoptosis or promotion of the cell cycle, cell apoptosis was assessed after FOXK1 was silenced; however, no significant effect was observed.…”

Section: Discussionmentioning

confidence: 99%

FOXK1 promotes glioblastoma proliferation and metastasis through activation of Snail transcription

Huang

Zhu

et al. 2018

Exp Ther Med

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Abstract. Forkhead box K1 (FOXK1) has been identified to have a crucial function in development and oncogenesis. However, its role in glioblastoma has remained largely elusive and was therefore assessed in the present study. In human glioblastoma multiforme (GBM) tissue samples, FOXK1 was determined to be highly expressed compared with adjacent normal tissue samples. In addition, high levels of FOXK1 were detected in the T98G and LN18 GBM cell lines as compare with those in normal human astrocytes. Of note, high expression of FOXK1 was revealed to be associated with metastasis and tumor size. Loss-and gain-of-function experiments were then performed to determine whether FOXK1 regulates epithelial to mesenchymal transition (EMT) and cell proliferation. Knockdown of FOXK1 significantly suppressed EMT and metastasis of GBM cells, while ectopic expression of FOXK1 promoted them. A luciferase reporter assay and a chromatin immunoprecipitation assay revealed that FOXK1 activated the transcription of Snail. In addition, as the results indicated that FOXK1 promotes GBM cell proliferation, the potential effect of FOXK1 on the cell cycle and apoptosis were further assessed. While FOXK1 had no effect on apoptosis, it promoted cell proliferation via enhancing the S-phase population. In brief, the present study indicated that FOXK1 acts as an oncogene with a key function in glioblastoma cell proliferation and EMT.

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FOXK1 interaction with FHL2 promotes proliferation, invasion and metastasis in colorectal cancer

Cited by 56 publications

References 35 publications

Long non‑coding RNA LINC01503 promotes colorectal cancer cell proliferation and invasion by regulating miR‑4492/FOXK1 signaling

Long non‑coding RNA LINC01503 promotes colorectal cancer cell proliferation and invasion by regulating miR‑4492/FOXK1 signaling

Snail/FOXK1/Cyr61 Signaling Axis Regulates the Epithelial–Mesenchymal Transition and Metastasis in Colorectal Cancer

FOXK1 promotes glioblastoma proliferation and metastasis through activation of Snail transcription

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