Identification of hypoxia-regulated angiogenic genes in colorectal cancer

Zong, Shaoqi; Li, Wen; Li, Hongjia; Han, Susu; liu, Shanshan; Shi, Qi; Hou, Fenggang

doi:10.1016/j.bbrc.2017.08.169

Cited by 19 publications

(21 citation statements)

References 34 publications

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“…The mechanism whereby TCL regulates CRC metastasis remains an open question. Hypoxia can stimulate colorectal cancer cell migration and invasion by promoting angiogenesis 31 , epithelial-mesenchymal transition (EMT) 4 , and cancer stem cell (CSC) self-renewal 32 . It has been previously demonstrated that TCL blockade leads to failed angiogenesis during breast cancer metastasis 18 .…”

Section: Discussionmentioning

confidence: 99%

Epigenetic activation of the small GTPase TCL contributes to colorectal cancer cell migration and invasion

et al. 2020

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TC10-like (TCL) is a small GTPase that has been implicated in carcinogenesis. Elevated TCL expression has been observed in many different types of cancers although the underlying epigenetic mechanism is poorly understood. Here we report that TCL up-regulation was associated with high malignancy in both human colorectal cancer biopsy specimens and in cultured colorectal cancer cells. Hypoxia, a pro-metastatic stimulus, up-regulated TCL expression in HT-29 cells. Further studies revealed that myocardin-related transcription factor A (MRTF-A) promoted migration and invasion of HT-29 cells in a TCL-dependent manner. MRTF-A directly bound to the proximal TCL promoter in response to hypoxia to activate TCL transcription. Chromatin immunoprecipitation (ChIP) assay showed that hypoxia stimulation specifically enhanced acetylation of histone H4K16 surrounding the TCL promoter, which was abolished by MRTF-A depletion or inhibition. Mechanistically, MRTF-A interacted with and recruited the H4K16 acetyltransferase hMOF to the TCL promoter to cooperatively regulate TCL transcription. hMOF depletion or inhibition attenuated hypoxia-induced TCL expression and migration/invasion of HT-29 cells. In conclusion, our data identify a novel MRTF-A-hMOF-TCL axis that contributes to colorectal cancer metastasis.

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Section: Discussionmentioning

confidence: 99%

Epigenetic activation of the small GTPase TCL contributes to colorectal cancer cell migration and invasion

et al. 2020

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“…To date, numerous studies have suggested that EMT is a key process in tumor metastasis. Hypoxia induces EMT via the HIF-dependent upregulation of transcription repressors of E-cadherin ( 12 ). Meanwhile, increasing evidence has addressed the molecular mechanisms underlying the reversal of EMT to exert anti-metastasis effects ( 26 ).…”

Section: Discussionmentioning

confidence: 99%

“…Inactivated Akt protein promotes cell survival via the phosphorylation and inactivation of several targets, including Caspase-3 and caspase-9, and regulates cell cycle progression through a reduction in the expression of cyclin-dependent kinase inhibitors p21 waf/cip1 and p27 ( 10 ). Indeed, studies have shown that PI3K/Akt/mTOR can regulate hypoxia-inducible factor-1α (HIF-1α) ( 11 ), a critical mediator of the physiological response to hypoxia, and its dysregulation can promote tumor angiogenesis and metastasis ( 12 ).…”

Section: Introductionmentioning

confidence: 99%

Bufalin suppresses the proliferation and metastasis of renal cell carcinoma by inhibiting the PI3K/Akt/mTOR signaling pathway

et al. 2018

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Bufalin, one of the active ingredients of the Chinese drug Chan su, exhibits significant antitumor activity against various cancer types. However, the role of bufalin in renal cell carcinoma (RCC) remains unclear. In the present study, it was demonstrated that bufalin inhibited cell proliferation, blocked the cell cycle in the G2/M phase, and reduced the metastasis of human RCC ACHN cells via the upregulation of p21waf/cip1 and E-cadherin and the downregulation of cyclin dependent kinase 1, cyclin B1, N-cadherin, and hypoxia-inducible factor-1α (HIF-1α). Further mechanistic study revealed that bufalin reduced the expression of phosphorylated (phospho)-Akt and phospho-mammalian target of rapamycin (mTOR). Moreover, HIF-1α expression may be regulated through the inhibition of the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mTOR signaling pathway. Thus, the present results suggest that bufalin induces cell cycle arrest and suppresses metastasis; this process may be associated with the PI3K/Akt/mTOR signaling pathway. Accordingly, it is suggested that bufalin is a therapeutic agent for RCC.

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“…Microarray analysis has been applied to investigate the processes involved in CRC, as it is an effective tool for detecting general genetic alterations in the study of oncology (23,24). The most obvious finding to emerge from the analysis was the enhanced expression of CXCL11 in both CRC and colorectal adenomas, even up to 4-fold higher compared with normal tissues.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‑144 mediates chronic inflammation and tumorigenesis in colorectal cancer progression via regulating C‑X‑C motif chemokine ligand 11

Han

Feng

Yu³

et al. 2018

Exp Ther Med

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Colorectal cancer (CRC) is one of the most common malignancies worldwide. The aim of the present study was to investigate the expression of microRNA-144 (miR-144) and C-X-C motif chemokine ligand 11 (CXCL11) in CRC and their association. Data from Gene Expression Omnibus (GEO) DataSets were analyzed to obtain the expression profile of CXCL11 in CRC. Subsequently, serum samples were collected from 65 subjects, including 39 patients with CRC and 26 controls; CRC and adjacent normal tissues were collected from all 39 CRC patients and the expression of CXCL11 was measured in these specimens. After searching for the potential regulator of CXCL11 through bioinformatics analysis, the levels of miR-144 in the clinical specimens were also detected. Finally, the regulatory association between miR-144 and CXCL11 was certified via the dual-luciferase reporter assay. Microarray data and bioinformatics analysis demonstrated that CXCL11 was significantly upregulated in CRC tissues and miR-144 was a potential regulator of CXCL11. In line with this finding, the expression of CXCL11 was significantly increased in the serum and tumor samples of patients with CRC, while that of miR-144 was downregulated. Dual-luciferase reporter assay revealed that miR-144 directly targets the 3′-untranslated region of CXCL11 mRNA to regulate its expression. These results demonstrated that enhanced CXCL11 expression in patients with CRC was associated with reduced miR-144 expression. The results of the present study may indicate a novel regulatory role of miR-144 in CRC through CXCL11 downregulation.

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Identification of hypoxia-regulated angiogenic genes in colorectal cancer

Cited by 19 publications

References 34 publications

Epigenetic activation of the small GTPase TCL contributes to colorectal cancer cell migration and invasion

Epigenetic activation of the small GTPase TCL contributes to colorectal cancer cell migration and invasion

Bufalin suppresses the proliferation and metastasis of renal cell carcinoma by inhibiting the PI3K/Akt/mTOR signaling pathway

MicroRNA‑144 mediates chronic inflammation and tumorigenesis in colorectal cancer progression via regulating C‑X‑C motif chemokine ligand 11

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