scholarly journals miR-23a-3p is a Key Regulator of IL-17C-Induced Tumor Angiogenesis in Colorectal Cancer

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1363 ◽  
Author(s):  
Yunna Lee ◽  
Su Jin Kim ◽  
Jieun Choo ◽  
Gwangbeom Heo ◽  
Jin-Wook Yoo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Growth ◽  
Tumor Angiogenesis ◽  
Ex Vivo ◽  
Underlying Mechanism ◽  
Vegf Receptor ◽  
Invasion And Migration ◽  
Novel Target ◽  
And Migration

MicroRNAs (miRNAs) have emerged as key players in tumor angiogenesis. Interleukin-17C (IL-17C) was identified to promote colorectal cancer (CRC) progression. Therefore, we aimed to investigate the effect of IL-17C on tumor angiogenesis, the involvement of miR-23a-3p in IL-17C signaling, and the direct target gene of miR-23a-3p in CRC. In vitro and ex vivo angiogenesis, a mouse xenograft experiment, and immunostaining were performed to test the effect of IL-17C on tumor angiogenesis. ELISA, quantitative real time PCR, and gene silencing were used to uncover the underlying mechanism. IL-17C induced angiogenesis of intestinal endothelial cells, subsequently enhancing cell invasion and migration of DLD-1 cells. IL-17C-stimulated DLD-1 cells produced vascular endothelial growth factor (VEGF) to enhance angiogenesis. Moreover, IL-17C markedly accelerated xenograft tumor growth, which was manifested by substantially reduced tumor growth when treated with the VEGF receptor 2 inhibitor Ki8751. Accordingly, Ki8751 suppressed the expression of IL-17C-stimulated PECAM and VE-cadherin in xenografts. Furthermore, IL-17C activated STAT3 to increase the expression of miR-23a-3p that suppressed semaphorin 6D (SEMA6D) expression, thereby permitting VEGF production. Taken together, our study demonstrates that IL-17C promotes tumor angiogenesis through VEGF production via a STAT3/miR-23a-3p/SEMA6D axis, suggesting its potential as a novel target for anti-CRC therapy.

scholarly journals Degradation of long non-coding RNA-CIR decelerates proliferation, invasion and migration, but promotes apoptosis of osteosarcoma cells

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Shiwei Liu ◽  
Jingchao Li ◽  
Liang Kang ◽  
Yueyang Tian ◽  
Yuan Xue
Keyword(s):  
Tumor Growth ◽  
Osteosarcoma Cell ◽  
Loss Of Function ◽  
Osteosarcoma Cells ◽  
Invasion And Migration ◽  
Normal Tissues ◽  
Novel Target ◽  
And Migration

Abstract Background Over the years, long non-coding RNAs (lncRNAs) have been clarified in malignancies, this research was focused on the role of lncRNA cartilage injury-related (lncRNA-CIR) in osteosarcoma cells. Methods LncRNA-CIR expression in osteosarcoma tissues and cells, and adjacent normal tissues and normal osteoblasts was determined, then the relations between lncRNA-CIR expression and the clinicopathological features, and between lncRNA-CIR expression and the prognosis of osteosarcoma patients were analyzed. Moreover, the MG63 and 143B cells were treated with silenced or overexpressed lncRNA-CIR, and then the proliferation, invasion, migration and apoptosis of the cells were evaluated by gain- and loss-of-function approaches. The tumor growth, and proliferation and apoptosis of osteosarcoma cells in vivo were observed by subcutaneous tumorigenesis in nude mice. Results We have found that lncRNA-CIR was up-regulated in osteosarcoma tissues and cells, which was respectively relative to adjacent normal tissues and normal osteoblasts. The expression of lncRNA-CIR was evidently correlated with disease stages, distant metastasis and differentiation of osteosarcoma patients, and the high expression of lncRNA-CIR indicated a poor prognosis. Furthermore, the reduction of lncRNA-CIR could restrict proliferation, invasion and migration, but promote apoptosis of osteosarcoma cells in vitro. Meanwhile, inhibited lncRNA-CIR also restrained tumor growth and osteosarcoma cell proliferation, whereas accelerated apoptosis of osteosarcoma cells in vivo. Conclusion We have found in this study that the inhibited lncRNA-CIR could decelerate proliferation, invasion and migration, but accelerate apoptosis of osteosarcoma cells, which may provide a novel target for osteosarcoma treatment.

scholarly journals HDAC3 deteriorates colorectal cancer progression via microRNA-296-3p/TGIF1/TGFβ axis

2020 ◽  
Vol 39 (1) ◽  
Author(s):  
Jinxiao Li ◽  
Man Hu ◽  
Na Liu ◽  
Huarong Li ◽  
Zhaomin Yu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Growth ◽  
Luciferase Reporter ◽  
Invasion And Migration ◽  
Induction Of Apoptosis ◽  
And Migration ◽  
Related Proteins ◽  
Tgfβ Pathway

Abstract Background The mechanism of histone deacetylase 3 (HDAC3) in colorectal cancer (CRC) has already been discussed. However, the feedback loop of HDAC3/microRNA (miR)-296-3p and transforming growth factor β-induced factor 1 (TGIF1) in CRC has not been explained clearly. Thus, the mainstay of this study is to delve out the mechanism of this axis in CRC. Methods To demonstrate that HDAC3 regulates the miR-296-3p/TGIF1/TGFβ axis and is involved in CRC progression, a series of cell biological, molecular and biochemical approaches were conducted from the clinical research level, in vitro experiments and in vivo experiments. These methods included RT-qPCR, Western blot assay, cell transfection, MTT assay, EdU assay, flow cytometry, scratch test, Transwell assay, dual luciferase reporter gene assay, chromatin immunoprecipitation, nude mouse xenograft, H&E staining and TUNEL staining. Results Higher HDAC3 and TGIF1 and lower miR-296-3p expression levels were found in CRC tissues. HDAC3 was negatively connected with miR-296-3p while positively correlated with TGIF1, and miR-296-3p was negatively connected with TGIF1. Depleted HDAC3 elevated miR-296-3p expression and reduced TGIF1 expression, decreased TGFβ pathway-related proteins, inhibited CRC proliferation, invasion, and migration in vitro and slowed down tumor growth and induction of apoptosis in vivo, which were reversed by miR-296-3p knockdown. Restored miR-296-3p suppressed TGIF1 and reduced TGFβ pathway-related proteins, inhibited CRC proliferation, invasion, and migration in vitro and slowed down tumor growth and induction of apoptosis in vivo, which were reversed by TGIF1 overexpression. Conclusion This study illustrates that down-regulation of HDAC3 or TGIF1 or up-regulation of miR-296-3p discourages CRC cell progression and slows down tumor growth, which guides towards a novel direction of CRC treatment.

scholarly journals Annexin A2 Coordinates STAT3 to Regulate the Invasion and Migration of Colorectal Cancer CellsIn Vitro

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Dianhui Xiu ◽  
Lin Liu ◽  
Fengli Qiao ◽  
Haishan Yang ◽  
Lu Cui ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Annexin A2 ◽  
Migration And Invasion ◽  
Invasion And Migration ◽  
Protein Levels ◽  
And Migration

The present study aimed to reveal the expression of STAT3 and Anxa 2 in CRC specimens and to investigate the effects of STAT3 and Anxa 2 signaling on the proliferation, invasion, and migration in CRC Caco-2 cells. Results demonstrated that both Anxa 2 and STAT3 were highly expressed in CRC specimens in both mRNA and protein levels, with or without phosphorylation (Tyrosine 23 in Anxa 2 and Tyrosine 705 in STAT3). And the upregulated Anxa 2 promoted the phosphorylation of STAT3 (Tyrosine 705) in CRC Caco-2 cells. The upregulated Anxa 2 promoted the proliferation, migration, and invasion of Caco-2 cells in vitro. Moreover, the STAT3 knockdown also repressed the proliferation, migration, and invasion of Caco-2 cells. In conclusion, the overexpressed Annexin A2 regulated the proliferation, invasion, and migration in CRC cells in an association with STAT3.

scholarly journals Synergistic antitumor effect of 5-fluorouracil with the novel LSD1 inhibitor ZY0511 in colorectal cancer

2020 ◽  
Vol 12 ◽  
pp. 175883592093742
Author(s):  
Wen Peng ◽  
Huaqing Zhang ◽  
Shisheng Tan ◽  
Yan Li ◽  
Yang Zhou ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Antitumor Effect ◽  
Underlying Mechanism ◽  
Synergistic Antitumor Effect ◽  
Anticancer Effects ◽  
Potential Marker ◽  
And Migration ◽  
Induced Apoptosis

Background: Lysine-specific histone demethylase 1 (LSD1) is a potential target of cancer therapy. In the present study, we aimed to investigate the combined antitumor activity of a novel LSD1 inhibitor (ZY0511) with 5-fluorouracil (5-FU) and elucidate the underlying mechanism in colorectal cancer (CRC). Methods: We evaluated LSD1 expression in CRC tissues from patients who received 5-FU treatment. The synergistic antitumor effect of 5-FU with ZY0511 against human CRC cells was detected both in vitro and in vivo. The underlying mechanism was explored based on mRNA sequencing (mRNA-seq) technology. Results: Overexpression of LSD1 was observed in human CRC tissues, and correlated with CRC development and 5-FU resistance. ZY0511, a novel LSD1 inhibitor, effectively inhibited CRC cells proliferation, both in vitro and in vivo. Notably, the combination of ZY0511 and 5-FU synergistically reduced CRC cells viability and migration in vitro. It also suppressed Wnt/β-catenin signaling and DNA synthesis pathways, which finally induced apoptosis of CRC cells. In addition, the combination of ZY0511 with 5-FU significantly reduced CRC xenograft tumor growth, along with lung and liver metastases in vivo. Conclusions: Our findings identify LSD1 as a potential marker for 5-FU resistance in CRC. ZY0511 is a promising candidate for CRC therapy as it potentiates 5-FU anticancer effects, thereby providing a new combinatorial strategy for treating CRC.

Knockdown of TPPP3 to inhibit cell proliferation and invasion in human colorectal cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e23006-e23006 ◽  
Author(s):  
Yintao Li ◽  
Jinming Yu
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Protein Family ◽  
Migration And Invasion ◽  
Clinicopathologic Characteristics ◽  
Invasion And Migration ◽  
Protein Levels ◽  
Angiogenesis Assay ◽  
And Migration

e23006 Background: Tubulin Polymerization Promoting Protein Family Member 3, TPPP3, a member of the TPPP protein family, has been reported to play important roles in initiation and progression of human cancers, such as lung cancer. However, the expression and underlying function of TPPP3 in colorectal cancer (CRC) have not yet been fully clarified. Methods: In this study, the mRNA and protein levels of TPPP3 in 96 clinical CRC specimens were determined by RT-PCR and immunohistochemistry. The relation between TPPP3 expression and clinicopathologic characteristics and overall survival (OS) were evaluated. TPPP3 was stably knockdowned by shRNA. In addition, CCK-8、Colony formation、Flow cytometric、Transwell and Angiogenesis assay were to examine the biological function of TPPP3 in CRC cells in vitro. Results: We show that TPPP3 was significantly increased in CRC tissues and associated with aggressive factors and poor patient survival. Further experiments showed that knockdown of TPPP3 inhibited cell proliferation, migration and invasion and induced cell apoptosis in vitro. In addition, TPPP3 silencing resulted in a decrease of angiogenesis and S phase fraction. And TPPP3 significantly affected the invasion and migration of CRC cells via the expression of MMP-9, Rac-1 and E-cadherin. Conclusions: Our results suggested that TPPP3 played an important role in CRC progress and might serve as novel therapeutic targets for CRC treatment.

scholarly journals A Chemerin Peptide Analog Stimulates Tumor Growth in Two Xenograft Mouse Models of Human Colorectal Carcinoma

Cancers ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 125
Author(s):  
Justa Friebus-Kardash ◽  
Petra Schulz ◽  
Sandy Reinicke ◽  
Cordula Karthaus ◽  
Quirino Schefer ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Cell Lines ◽  
Colony Formation ◽  
Ex Vivo ◽  
Three Dimensional ◽  
Peptide Analog ◽  
Scratch Wound ◽  
Tumorigenesis And Progression ◽  
And Migration

Background: Chemerin plasma concentration has been reported to be positively correlated with the risk of colorectal cancer. However, the potential regulation of CRC tumorigenesis and progression has not yet been investigated in an experimental setting. This study addresses this hypothesis by investigating proliferation, colony formation, and migration of CRC cell lines in vitro as well as in animal models. Methods: In vitro, microscopic assays to study proliferation, as well as a scratch-wound assay for migration monitoring, were applied using the human CRC cell lines HCT116, HT29, and SW620 under the influence of the chemerin analog CG34. The animal study investigated HCT116-luc and HT29-luc subcutaneous tumor size and bioluminescence during treatment with CG34 versus control, followed by an ex-vivo analysis of vessel density and mitotic activity. Results: While the proliferation of the three CRC cell lines in monolayers was not clearly stimulated by CG34, the chemerin analog promoted colony formation in three-dimensional aggregates. An effect on cell migration was not observed. In the treatment study, CG34 significantly stimulated both growth and bioluminescence signals of HCT116-luc and HT29-luc xenografts. Conclusions: The results of this study represent the first indication of a tumor growth-stimulating effect of chemerin signaling in CRC.

scholarly journals GRHL3 Promotes Tumor Growth and Metastasis via the MEK Pathway in Colorectal Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Lin Tan ◽  
Weiming Qu ◽  
Dajun Wu ◽  
Minji Liu ◽  
Qian Wang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Growth ◽  
Underlying Mechanism ◽  
Promoting Effect ◽  
Promote Tumor Growth ◽  
Proliferation And Metastasis ◽  
Tumor Growth And Metastasis ◽  
Cell Proliferation And Metastasis

GRHL3 is a factor associated with a tumor, of which the molecular mechanism remains a further investigation. We explored the underlying mechanism of tumor-promoting effect of GRHL3 in colorectal cancer (CRC), which is involved in the MEK1/2 pathway. The expression of GRHL3 was measured in CRC and adjacent normal tissue using qPCR and immunohistochemical staining. Lentivirus-mediated knockdown expression of GRHL3 was performed in the CRC cell line HT29. Cell proliferation and metastasis were assayed in vitro, and tumorigenicity was investigated in vivo. We found higher GRHL3 expression in colorectal cancer, which was negatively correlated with patients’ prognosis. Results from studies in vitro and in vivo indicated that downregulation of GRHL3 expression inhibited tumor growth and metastasis and inhibited the activation of the MEK1/2 pathway. The effect of GRHL3 downexpression was the same as that of MEK1/2 antagonists on suppression of tumor growth and metastasis. Our results suggested that GRHL3 may act as an oncogene to promote tumor growth and metastasis via the MEK pathway in colorectal cancer.

scholarly journals IRF2 Destabilizes Oncogenic KPNA2 to Modulate the Tumorigenesis of Osteosarcoma via Regulating NF-κB/p65

2021 ◽  
Author(s):  
Shuchi Xia ◽  
Yiqun Ma
Keyword(s):  
Tumor Growth ◽  
Western Blot ◽  
Underlying Mechanism ◽  
Normal Human ◽  
And Migration ◽  
Oncogenic Function ◽  
Opposing Effect ◽  
Proliferation And Migration

Abstract Background: Osteosarcomas (OS) are the most frequent primary malignant bone tumor. Emerging evidence revealed that karyopherin alpha 2 (KPNA2) was strongly associated with the tumorigenesis and development of numerous human cancers. The aim of the present study was to investigate the expression pattern, biological functions and underlying mechanism of KPNA2 in OS. Methods: Bioinformatics TFBIND online was applied to forecast the transcription factor (TF) binding sites in the promoter region of KPNA2. The expression profile of KPNA2 in OS tissues were firstly assessed using TARGET dataset. The expression of KPNA2 in clinical OS samples and normal human adjacent samples were analyzed by RT-qPCR and western blot. CCK8, colony formation, wound-healing, and Transwell assays were used to assess cell viability, proliferation and migration in vitro, and in vivo experiments were performed to explore the effects of KPNA2 and interferon regulatory factor-2 (IRF2) on tumor growth. In addition, the correlation between IRF2 and KPNA2, and their roles on the NF-κB/p65 was investigated using chromatin immunoprecipitation (ChIP), RT-qPCR, western blot and dual-luciferase assays. Results: KPNA2 was obviously upregulated while IRF2 was significantly decreased in OS tissues and cell lines, as well as they were negatively correlated with each other. KPNA2 knockdown remarkably suppressed OS cell growth, migration, invasion in vitro and tumor growth in vivo, while IRF2 knockdown exerts an opposing effect. IRF2 binds to KPNA2 promoter to modulate the tumorigenic malignant phenotypes of OS via regulating NF-κB/p65 signaling. Conclusion: The present study demonstrated that KPNA2 performed the oncogenic function, possibly regulating tumorigenesis through NF-κB/p65 signaling pathway. Importantly, IRF2 was confirmed to serve a potential upstream TF of KPNA2 involving in the regulation of NF-κB/p65 pathway in OS.

LPA-induced epithelial ovarian cancer (EOC) in vitro invasion and migration are mediated by VEGF receptor-2 (VEGF-R2)

2005 ◽  
Vol 97 (3) ◽  
pp. 870-878 ◽  
Author(s):  
John So ◽  
Feng-qiang Wang ◽  
Jason Navari ◽  
Jeremy Schreher ◽  
David A. Fishman
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Vegf Receptor ◽  
Invasion And Migration ◽  
In Vitro Invasion ◽  
And Migration

scholarly journals CDC5L Promotes hTERT Expression and Colorectal Tumor Growth

2017 ◽  
Vol 41 (6) ◽  
pp. 2475-2488 ◽  
Author(s):  
Jia Li ◽  
Ningning Zhang ◽  
Rui Zhang ◽  
Longmei Sun ◽  
Wendan Yu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Growth ◽  
Luciferase Reporter ◽  
Htert Expression ◽  
Human Telomerase Reverse Transcriptase ◽  
Cell Growth And Migration ◽  
And Migration ◽  
Human Telomerase

Background/Aims: Colorectal cancer (CRC) is the third leading cause of cancer-related death worldwide because the survival rate remains low. Cell division cycle 5-like (CDC5L) is highly expressed in some cancer cells, but the mechanism requires clarification. Human telomerase reverse transcriptase (hTERT) plays important roles in CRC. Methods: This study aimed to identify a link between CDC5L and hTERT and to determine their effects on the signaling pathways, migration and prognosis of CRC cells. We first treated LoVo cells with biotin-labeled hTERT and identified CDC5L. Then, pulldown and ChIP assays were used to verify whether CDC5L was a promoter of hTERT. The roles of CDC5L and hTERT in cell growth and migration were studied using siRNA in vivo and in vitro. 130 human CRC specimens were analyzed using immunohistochemistry. Western blot and wound scratch analyses were used to determine the signaling pathway for CDC5L-mediated activation of CRC growth and migration. Results: We identified CDC5L as a new hTERT promoter-binding protein. Clinically, CDC5L and hTERT expression levels were key factors in the prognosis of CRC patients. CDC5L knockdown inhibited tumor growth by down-regulating hTERT expression, and CDC5L was shown to be a transcriptional activator of hTERT in a luciferase reporter assay. Conclusion: Altogether, the above results demonstrated that CDC5L was positively correlated with hTERT as a key promoter of CRC cells. To some extent, our findings suggest that CDC5L may serve as a novel therapeutic target for human colorectal cancer.

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