scholarly journals MiR-106b-5p regulates the migration and invasion of colorectal cancer cells by targeting FAT4

2020 ◽  
Vol 40 (11) ◽  
Author(s):  
Min Pan ◽  
Qiuqiu Chen ◽  
Yusong Lu ◽  
Feifei Wei ◽  
Chunqiao Chen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Scratch Test ◽  
Underlying Mechanism ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Messenger Rnas ◽  
Colorectal Cancer Cells

Abstract MicroRNA-106b-5p (miR-106b-5p) is involved in the development of many cancers including colorectal cancer (CRC), and FAT4 is correlated with regulation of growth and apoptosis of cancer cells. The present study aimed to investigate the relation between FAT4 and miR-106b-5p and the underlying mechanism of the two on the development of CRC. Quantitative real-time PCR (qRT-PCR) assay and Western blot (WB) analysis were performed to detect the expressions of messenger RNAs (mRNAs), microRNAs (miRNAs) and proteins. The viability of CRC cells was detected by cell counting kit-8 (CCK-8). Scratch test and transwell assay were performed to measure the migration and invasion of CRC cell. Tumor angiogenesis was simulated by in vitro angiogenesis experiment. Dual-luciferase reporter assay was performed to verify the targeting relation between miR-106b-5p and FAT4. The study found that the expression of FAT4 was down-regulated and that of miR-106b-5p was up-regulated in CRC tissues. Overexpression of FAT4 resulted in decreased proliferation, migration, invasion and angiogenesis of CRC cells, whereas silencing of FAT4 led to the opposite results. In rescue experiment, miR-106b-5p partially reversed the function of FAT4 in CRC cells, thus playing a carcinogenic role by targeting FAT4 in the CRC cells.

scholarly journals Pals1 prevents Rac1-dependent colorectal cancer cell metastasis by inhibiting Arf6

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Simona Mareike Lüttgenau ◽  
Christin Emming ◽  
Thomas Wagner ◽  
Julia Harms ◽  
Justine Guske ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Migration ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Scaffolding Protein ◽  
Migration And Invasion ◽  
Tight Junction Formation ◽  
Cell Metastasis ◽  
Colorectal Cancer Cells

AbstractLoss of apical-basal polarity and downregulation of cell-cell contacts is a critical step during the pathogenesis of cancer. Both processes are regulated by the scaffolding protein Pals1, however, it is unclear whether the expression of Pals1 is affected in cancer cells and whether Pals1 is implicated in the pathogenesis of the disease.Using mRNA expression data and immunostainings of cancer specimen, we show that Pals1 is frequently downregulated in colorectal cancer, correlating with poorer survival of patients. We further found that Pals1 prevents cancer cell metastasis by controlling Rac1-dependent cell migration through inhibition of Arf6, which is independent of the canonical binding partners of Pals1. Loss of Pals1 in colorectal cancer cells results in increased Arf6 and Rac1 activity, enhanced cell migration and invasion in vitro and increased metastasis of transplanted tumor cells in mice. Thus, our data reveal a new function of Pals1 as a key inhibitor of cell migration and metastasis of colorectal cancer cells. Notably, this new function is independent of the known role of Pals1 in tight junction formation and apical-basal polarity.

scholarly journals MicroRNA-124 Regulates the Proliferation of Colorectal Cancer Cells by TargetingiASPP

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Kuijie Liu ◽  
Hua Zhao ◽  
Hongliang Yao ◽  
Sanlin Lei ◽  
Zhendong Lei ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Target Prediction ◽  
Inhibitory Effect ◽  
Luciferase Reporter ◽  
Luciferase Reporter Gene ◽  
Small Noncoding Rnas ◽  
Colorectal Cancer Cells ◽  
Microrna 124

MicroRNAs are a class of small, noncoding RNAs that function as critical regulators of gene expression by targeting mRNAs for translational repression or degradation. In this study, we demonstrate that expression of microRNA-124 (miR-124) is significantly downregulated in colorectal cancer tissues and cell lines, compared to the matched adjacent tissues. We identified and confirmed inhibitor of apoptosis-stimulating protein of p53 (iASPP) as a novel, direct target of miR-124 using target prediction algorithms and luciferase reporter gene assays. Overexpression of miR-124 suppressed iASPP protein expression, upregulated expression of the downstream signaling molecule nuclear factor-kappa B (NF-κB), and attenuated cell viability, proliferation, and colony formation in SW480 and HT-29 colorectal cancer cells in vitro. Forced overexpression ofiASPPpartly rescued the inhibitory effect of miR-124 on SW480 and HT29 cell proliferation. Taken together, these findings shed light on the role and mechanism of action of miR-124, indicate that the miR-124/iASPP axis can regulate the proliferation of colorectal cancer cells, and suggest that miR-124 may serve as a potential therapeutic target for colorectal cancer.

scholarly journals CSN8 is a key regulator in hypoxia-induced epithelial–mesenchymal transition and dormancy of colorectal cancer cells

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Songwen Ju ◽  
Feng Wang ◽  
Yirong Wang ◽  
Songguang Ju
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Epithelial Mesenchymal Transition ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Treatment Conditions ◽  
Colorectal Cancer Cells

AbstractHypoxic stress plays a pivotal role in cancer progression; however, how hypoxia drives tumors to become more aggressive or metastatic and adaptive to adverse environmental stress is still poorly understood. In this study, we revealed that CSN8 might be a key regulatory switch controlling hypoxia-induced malignant tumor progression. We demonstrated that the expression of CSN8 increased significantly in colorectal cancerous tissues, which was correlated with lymph node metastasis and predicted poor patient survival. CSN8 overexpression induces the epithelial-mesenchymal transition (EMT) process in colorectal cancer cells, increasing migration and invasion. CSN8 overexpression arrested cell proliferation, upregulated key dormancy marker (NR2F1, DEC2, p27) and hypoxia response genes (HIF-1α, GLUT1), and dramatically enhanced survival under hypoxia, serum deprivation, or chemo-drug 5-fluorouracil treatment conditions. In particular, silenced CSN8 blocks the EMT and dormancy processes induced by the hypoxia of 1% O2 in vitro and undermines the adaptive capacity of colorectal cancer cells in vivo. The further study showed that CSN8 regulated EMT and dormancy partly by activating the HIF-1α signaling pathway, which increased HIF-1α mRNA expression by activating NF-κB and stabilized the HIF-1α protein via HIF-1α de-ubiquitination. Taken together, CSN8 endows primary colorectal cancer cells with highly aggressive/metastatic and adaptive capacities through regulating both EMT and dormancy induced by hypoxia. CSN8 could serve as a novel prognostic biomarker for colorectal cancer and would be an ideal target of disseminated dormant cell elimination and tumor metastasis, recurrence, and chemoresistance prevention.

scholarly journals LPS Upregulated VEGFR-3 Expression Promote Migration and Invasion in Colorectal Cancer via a Mechanism of Increased NF-κB Binding to the Promoter of VEGFR-3

2016 ◽  
Vol 39 (5) ◽  
pp. 1665-1678 ◽  
Author(s):  
Guangwei Zhu ◽  
Qiang Huang ◽  
Wei Zheng ◽  
Yongjian Huang ◽  
Jin Hua ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Neutralizing Antibody ◽  
High Expression ◽  
Migration And Invasion ◽  
Colorectal Cancer Cells ◽  
Cancer Tissues ◽  
The Relationship

Background and Aim: Lipopolysaccharide(LPS) could promote the progression of colorectal cancer, but the specific regulatory mechanisms are largely unknown. So, this study aim to clarify the mechanisms that LPS upregulated VEGFR-3, which promotes colorectal cancer cells migration and invasion with a mechanism of increased NF-κB bind to the promoter of VEGFR-3. Methods: The present study examined the VEGFR-3 expression in colorectal cancer tissues and analyzed the relationship between the VEGFR-3 expression with clinical parameters. PCR, Western blot, CCK-8, colone formation assay, and Transwell assay detected that LPS promoted the migration and invasion and the role of VEGFR-3 in the process of colorectal carcinoma in vitro. Used the methods of promoter analysis, EMSA assay and ChIP assay to explore the mechanisms LPS increased the expression of VEGFR-3. Results: VEGFR-3 was significantly high expression in the colorectal cancer tissues. And the high expression was associated with the TNM stage and lymph node metastasis of colorectal cancer. LPS could promote the migration and invasion, which could be blocked by the neutralizing antibody IgG of VEGFR-3. And found that -159 nt to +65 nt was the crucial region of VEGFR-3 promoter. And detected that the NF-κB was important transcription factor for the VEGFR-3 promoter. And LPS could increase NF-κB binding to VEGFR-3 promoter and upregulated the expression of VEGFR-3 to exert biological functions. Conclusion: We have elucidated the relationship between LPS and the VEGFR-3 expression and revealed that VEGFR-3 play very important role in the process of LPS promoting the migration and invasion of colorectal cancer cells. Further illuminated the mechanism that LPS upregulated VEGFR-3 expression via increased NF-κB bind to the promoter of VEGFR-3.

scholarly journals circVAPA promotes the proliferation, migration and invasion of oral cancer cells through the miR-132/HOXA7 axis

2021 ◽  
Vol 49 (6) ◽  
pp. 030006052110132
Author(s):  
Hao Chen ◽  
Ye Zhang ◽  
Kankui Wu ◽  
Xiaoyong Qiu
Keyword(s):  
Oral Cancer ◽  
Cancer Cells ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Loss Of Function ◽  
Invasion And Migration ◽  
Oral Cancer Cells ◽  
And Migration

Objective To study the relationship between the circular RNA vesicle-associated membrane protein-associated protein A (circVAPA) and the pathogenesis of oral squamous cell carcinoma. Methods The expression of circVAPA was detected by RT-qPCR. In vitro loss-of-function experiments were performed in Cal-27 cells. The malignant phenotype of cells was evaluated by cell counting kit-8, clone formation and transwell assays. Luciferase reporter assays were used to assess the circVAPA/miR-132/homeobox A (HOXA) regulatory axis. Results circVAPA expression was significantly increased in oral cancer tissues and cells. The overall survival and progression-free survival of patients with oral cancer who exhibited high circVAPA expression were significantly shorter compared with those with low expression. circVAPA expression was closely related to tumor size, TNM stage and distant metastasis. circVAPA knockdown reduced the proliferation, invasion and migration of Cal-27 cells. MiR-132 was identified as a target of circVAPA in Cal-27 cells. Cotransfection with si-circVAPA and miR-132 inhibitor reversed the inhibitory effect of circVAPA knockdown on cell malignant phenotypes. HOXA7 was further identified as a downstream target of miR-132. Conclusion circVAPA is highly expressed in oral cancer, and its abnormal expression might affect the proliferation, invasion and migration of oral cancer cells by modulating the miR-132/HOXA7 signaling axis.

scholarly journals Long noncoding RNA MAPKAPK5-AS1 promotes colorectal cancer progression by cis-regulating the nearby gene MK5 and acting as a let-7f-1-3p sponge

2020 ◽  
Author(s):  
Ting Yang ◽  
Wei-Cong Chen ◽  
Pei-Cong Shi ◽  
Man-Ru Liu ◽  
Tao Jiang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Progression ◽  
Noncoding Rna ◽  
Vital Role ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Colorectal Cancer Progression ◽  
Molecular Therapeutic

Abstract Background: Long noncoding RNAs (lncRNAs) are considered critical regulators in cancers; however, the clinical significance and mechanisms of MAPKAPK5-AS1 (hereinafter referred to as MK5-AS1) in colorectal cancer (CRC) remain mostly unknown.Methods: In this study, quantitative real-time PCR (qPCR) and western blotting were utilized to detect the levels of MK5-AS1, let-7f-1-3p and MK5 (MAPK activated protein kinase 5) in CRC tissues and cell lines. The biological functions of MK5-AS1, let-7f-1-3p and MK5 in CRC cells were explored using Cell Counting Kit-8 (CCK8), colony formation and transwell assays. The potential mechanisms of MK5-AS1 were evaluated by RNA pull-down, RNA immunoprecipitation (RIP), dual luciferase reporter assay, chromatin immunoprecipitation (CHIP) and bioinformatics analysis. The effects of MK5-AS1 and MK5 on CRC were investigated by a xenotransplantation model. Results: We confirmed that MK5-AS1 was significantly increased in CRC tissues. Knockdown of MK5-AS1 suppressed cell migration and invasion in vitro and inhibited lung metastasis in mice. Mechanistically, MK5-AS1 regulated SNAI1 expression by sponging let-7f-1-3p and cis-regulated the adjacent gene MK5. Moreover, MK5-AS1 recruited RBM4 and eIF4A1 to promote the translation of MK5. Our study verified that MK5 promoted the phosphorylation of c-Jun, which activated the transcription of SNAI1 by directly binding to its promoter. Conclusions: MK5-AS1 cis-regulated the nearby gene MK5 and acted as a let-7f-1-3p sponge, playing a vital role in CRC tumorigenesis. This study could provide novel insights into molecular therapeutic targets of CRC.

scholarly journals LINC00659 Regulates Colorectal Cancer Migration and Invasion by Targeting miR-485-5p/HOXC13 Axis

2021 ◽  
Author(s):  
Haojie Yang ◽  
Jihong Fu ◽  
Guangyang Jiao ◽  
Yilian Zhu ◽  
Yilin Han ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Noncoding Rna ◽  
In Vitro Models ◽  
Migration And Invasion ◽  
Validation Experiment ◽  
Colorectal Cancer Cells

Abstract BackgroundLong noncoding RNA LINC00659 has been reported to be involved in the carcinogenesis and progression of colorectal cancer. However, the molecular mechanism remains ambiguous.MethodsIn this study, we found that HOXC13 expression was closely related with colorectal cancer and positively correlated with LINC00659 via bioinformatics analysis and clinical validation experiment. Meanwhile, miR-485-5p was identified as an overlapped target miRNA. To further dissect whether miR-485-5p and HOXC13 were involved in LINC00659 mediated colorectal cancer progression, we first established human in vitro models and demonstrated that LINC00659 could directly bind with miR-485-5p and knockdown of LINC00659 upregulated the expression of miR-485-5p. In addition, knockdown of LINC00659 inhibited the expression of HOXC13 by targeting miR-485-5p. Finally, we analyzed the effect of LINC00659/miR-485-5p/HOXC13 axis on tumor growth. Both animal model and in vitro model confirmed the anti-tumor effect of knockdown of LINC00659, which could suppress the colorectal cancer cell viability, migration and invasion by targeting miR-485-5p/HOXC13 axis. Results1. LINC00659 and HOXC13 are highly expressed in colorectal cancer cells.2. miRNA-485-5p is lowly expressed in colorectal cancer cells.3. LINC00659/miR-485-5p/HOXC13 axis is important for colorectal cancer cells.4. LINC00659 promotes tumor growth by sponging miR-485-5p.ConclusionsOur study uncovered a novel mechanism of LINC00659 in the progression of colorectal cancer and provided a potential strategy for the treatment and diagnose of colorectal cancer.

scholarly journals LncRNA testis-specific transcript, Y-linked 15 (TTTY15) promotes proliferation, migration and invasion of colorectal cancer cells via regulating miR-29a-3p/DVL3 axis

2020 ◽  
pp. 1-11
Author(s):  
Xiao-Ying Zheng ◽  
Ming-Zheng Cao ◽  
Ying Ba ◽  
Yue-Feng Li ◽  
Jun-Ling Ye
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Colony Formation ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Qrt Pcr ◽  
Specific Transcript ◽  
Gene Assay ◽  
Colorectal Cancer Cells ◽  
Proliferation And Metastasis

BACKGROUND: Long non-coding RNA testis-specific transcript, Y-linked 15 (TTTY15) is oncogenic in prostate cancer, however its expression and function in colorectal cancer remain largely unknown. METHODS: Paired colorectal cancer samples/adjacent tissues were collected, and the expression levels of TTTY15, miR-29a-3p and disheveled segment polarity protein 3 (DVL3) were examined by quantitative real-time polymerase chain reaction (qRT-PCR); TTTY15 shRNA and overexpression plasmids were transfected into HT29 and HCT-116 cell lines using lipofectamine reagent, respectively; the proliferation and colony formation were detected by CCK-8 assay and plate colony formation assay; qRT-PCR and Western blot were used to analyze the changes of miR-29a-3p and DVL3; dual-luciferase reporter gene assay was used to determine the regulatory relationships between miR-29a-3p and TTTY15, miR-29a-3p and DVL3. RESULTS: TTTY15 was significantly up-regulated in cancerous tissues of colorectal cancer samples, positively correlated with the expression of DVL3, while negatively correlated with the expression of miR-29a-3p. After TTTY15 shRNAs were transfected into colorectal cancer cells, the proliferation and metastasis of cancer cells were significantly inhibited, while TTTY15 overexpression had opposite biological effects. TTTY15 shRNA could reduce the expression of DVL3 on both mRNA and protein levels, and the luciferase activity of TTTY15 sequence was also inhibited by miR-29a-3p. DVL3 was also validated as a target gene of miR-29a-3p, and it could be repressed by miR-29a-3p mimics or TTTY15 shRNA. CONCLUSION: TTTY15 is abnormally upregulated in colorectal cancer tissues, and it can modulate the proliferation and metastasis of colorectal cancer cells. It functions as the ceRNA to regulate the expression of DVL3 by sponging miR-29a-3p.

scholarly journals Circular RNA 100146 Promotes Colorectal Cancer Progression by miR-149/HMGA2 Axis

2020 ◽  
Author(s):  
Kunpeng Liu ◽  
Yuhua Mou ◽  
Xiufang Shi ◽  
Tingkun Liu ◽  
Zhanfeng Chen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Progression ◽  
Xenograft Model ◽  
Underlying Mechanism ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Circular Rnas ◽  
Western Blot Assay

Aim: Colorectal cancer (CRC) has developed into the third leading reason of cancer-associated death worldwide. Studies has confirmed that circular RNAs (circRNAs) sponge microRNAs (miRNAs) to regulate the function of downstream genes. This study aimed to expound the underlying mechanism of circRNA 100146 in CRC. Methods: The expression of circRNA 100146, miR-149 and high mobility group A2 (HMGA2) was detected by quantitative real time PCR (RT-qPCR). A series of bio-functional effects (cell viability, apoptosis, migration/invasion) were evaluated by methyl thiazolyl tetrazolium (MTT), flow cytometry, transwell. Protein level was measured by Western blot assay. The xenograft model was established for in vivo experiments. The interactions among circRNA 100146, miR-149 and HMGA2 were evaluated by dual-luciferase reporter assay, RNA immunoprecipitation assays, or RNA pulldown assay. Results: CircRNA 100146 was upregulated in CRC tissues and cells. CircRNA 100146 knockdown inhibited cell proliferation, promoted apoptosis and suppressed migration and invasion in vitro, and impeded tumor growth in vivo. Also, miR-149 was negalitively regulated by circRNA 100146, and targeted to HMGA2 and mediated its expression. Moreover, miR-149 interference abrogated the activities of silenced circRNA 100146 in proliferation, apoptosis, migration and invasion. Furthermore, HMGA2 overexpression abated the effects above caused by circRNA 100146 silencing, while the mutant on miR-149 binding sites in HMGA2 3’UTR lead to it losing this ability. Conclusion: CircRNA 100146 knockdown repressed proliferation, enhanced apoptosis and hindered migration and invasion in SW620 and SW480 cells through targeting miR-149/HMGA2 axis.

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