Molecular Mechanisms by Which S100A4 Regulates the Migration and Invasion of PGCCs With Their Daughter Cells in Human Colorectal Cancer

Background: Colorectal cancer (CRC) is the second leading cause of death worldwide, and distant metastasis is responsible for the poor prognosis in patients with advanced-stage CRC. RPS24 (ribosomal protein S24) as a ribosomal protein, multiple transcript variant encoding different isoforms have been found for this gene. Our previous studies have demonstrated that RPS24 is overexpressed in CRC. However, the mechanisms underlying the role of RPS24 in tumor development have not been fully defined. Methods: Expression of RPS24 isoforms and lncRNA MVIH in CRC tissues and cell lines were quantified by real-time PCR or western blotting assay. Endothelial tube formation assay was performed to determine the effect of RPS24 on tumor angiogenesis. The cell viability of HUVEC was determined by MTT assay, and the migration and invasion ability of HUVEC were detected by transwell assay. PGK1 secretion was tested with a specific ELISA kit. Results: Here, we found that RPS24c isoform was a major contributor to tumor angiogenesis, a vital process in tumor growth and metastasis. Real-time PCR revealed that RPS24c isoform was highly expressed in CRC tissues, while other isoforms are present in both normal and CRC tissues with no statistical difference. Moreover the change of RPS24 protein level is mainly due to the fluctuation of RPS24c. Furthermore, we observed that silencing RPS24c could decrease angiogenesis by inhibiting tubule formation, HUVEC cell proliferation and migration. Additionally, we investigated the molecular mechanisms and demonstrated that RPS24c mRNA interacted with lncRNA MVIH, the binding-interaction enhanced the stability of each other, thereby activated angiogenesis by inhibiting the secretion of PGK1. Conclusion: RPS24c facilitates tumor angiogenesis via the RPS24c/MVIH/PGK1 pathway in CRC. RPS24c inhibition may be a novel option for anti-vascular treatment in CRC.

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SPNS2 Downregulation Induces EMT and Promotes Colorectal Cancer Metastasis via Activating AKT Signaling Pathway

Frontiers in Oncology ◽

10.3389/fonc.2021.682773 ◽

2021 ◽

Vol 11 ◽

Author(s):

Lei Lv ◽

Qiyi Yi ◽

Ying Yan ◽

Fengmei Chao ◽

Ming Li

Keyword(s):

Colorectal Cancer ◽

Molecular Mechanisms ◽

Cancer Metastasis ◽

Epithelial Mesenchymal Transition ◽

Ectopic Expression ◽

Migration And Invasion ◽

Akt Inhibitor ◽

Colon Adenoma ◽

Mesenchymal Transition

Spinster homologue 2 (SPNS2), a transporter of S1P (sphingosine-1-phosphate), has been reported to mediate immune response, vascular development, and pathologic processes of diseases such as cancer via S1P signaling pathways. However, its biological functions and expression profile in colorectal cancer (CRC) is elusive. In this study, we disclosed that SPNS2 expression, which was regulated by copy number variation and DNA methylation of its promoter, was dramatically upregulated in colon adenoma and CRC compared to normal tissues. However, its expression was lower in CRC than in colon adenoma, and low expression of SPN2 correlated with advanced T/M/N stage and poor prognosis in CRC. Ectopic expression of SPNS2 inhibited cell proliferation, migration, epithelial–mesenchymal transition (EMT), invasion, and metastasis in CRC cell lines, while silencing SPNS2 had the opposite effects. Meanwhile, measuring the intracellular and extracellular level of S1P after overexpression of SPNS2 pinpointed a S1P-independent model of SPNS2. Mechanically, SPNS2 led to PTEN upregulation and inactivation of Akt. Moreover, AKT inhibitor (MK2206) abrogated SPNS2 knockdown-induced promoting effects on the migration and invasion, while AKT activator (SC79) reversed the repression of migration and invasion by SPNS2 overexpression in CRC cells, confirming the pivotal role of AKT for SPNS2’s function. Collectively, our study demonstrated the suppressor role of SPNS2 during CRC metastasis, providing new insights into the pathology and molecular mechanisms of CRC progression.

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Cooperation of SRPK2, Numb and p53 in the malignant biology and chemosensitivity of colorectal cancer

Bioscience Reports ◽

10.1042/bsr20191488 ◽

2020 ◽

Vol 40 (1) ◽

Author(s):

Guosen Wang ◽

Weiwei Sheng ◽

Jingtong Tang ◽

Xin Li ◽

Jianping Zhou ◽

...

Keyword(s):

Colorectal Cancer ◽

Cell Migration ◽

Cancer Progression ◽

Molecular Mechanisms ◽

Migration And Invasion ◽

Chemical Agent ◽

Cell Migration And Invasion ◽

Agent Treatment ◽

Hct116 Cells

Abstract Serine-arginine protein kinase 2 (SRPK2) is aberrantly expressed in human malignancies including colorectal cancer (CRC). However, little is known about the molecular mechanisms, and the role of SRPK2 in chemosensitivity remains unexplored in CRC. We recently showed that SRPK2 promotes pancreatic cancer progression by down-regulating Numb and p53. Therefore, we investigated the cooperation between SRPK2, Numb and p53 in the cell migration, invasion and chemosensitivity of CRC in vitro. Here, we showed that SRPK2 expression was higher in CRC tumors than in nontumor tissues. SRPK2 expression was positively associated with clinicopathological characteristics of CRC patients, including tumor differentiation, T stage, N stage and UICC stage. Additionally, SRPK2 had no association with mutant p53 (mtp53) in SW480 and SW620 cells, but negatively regulated Numb and wild-type p53 (wtp53) in response to 5-fluorouracil or cisplatin treatment in HCT116 cells. Moreover, SRPK2, Numb and p53 coimmunoprecipitated into a triple complex with or without the treatment of 5-fluorouracil in HCT116 cells, and p53 knockdown reversed the up-regulation of wtp53 induced by SRPK2 silencing with chemical agent treatment. Furthermore, overexpression of SRPK2 increased cell migration and invasion and decreased chemosensitivity to 5-fluorouracil or cisplatin in HCT116 cells. Conversely, SRPK2 silencing decreased cell migration and invasion and increased chemosensitivity to 5-fluorouracil or cisplatin, yet these effects could be reversed by p53 knockdown under chemical agent treatment. These results thus reveal a novel role of SRPK2-Numb-p53 signaling in the progression of CRC and demonstrate that SRPK2 is a potential therapeutic target for CRC clinical therapy.

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Overexpression of secretagogin promotes cell apoptosis and inhibits migration and invasion of human SW480 human colorectal cancer cells

Biomedicine & Pharmacotherapy ◽

10.1016/j.biopha.2018.01.147 ◽

2018 ◽

Vol 101 ◽

pp. 342-347 ◽

Cited By ~ 1

Author(s):

Xiang-yi Yang ◽

Qiao-rui Liu ◽

Li-ming Wu ◽

Xu-lei Zheng ◽

Cong Ma ◽

...

Keyword(s):

Colorectal Cancer ◽

Cancer Cells ◽

Cell Apoptosis ◽

Migration And Invasion ◽

Human Colorectal Cancer ◽

Colorectal Cancer Cells ◽

Human Colorectal Cancer Cells

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CircABCC4 Regulates the Proliferation, Migration, and Invasion of Colorectal Cancer SW620 Cells by Targeting Micro RNA-216a-3p

Journal of Biomaterials and Tissue Engineering ◽

10.1166/jbt.2021.2605 ◽

2021 ◽

Vol 11 (3) ◽

pp. 548-552

Author(s):

Yiqian Li ◽

Haofeng Yuan ◽

Yibin Chen ◽

Baoqi Xu ◽

Yanhong Zhang

Keyword(s):

Colorectal Cancer ◽

Micro Rna ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Human Colorectal Cancer ◽

Cell Behaviors ◽

Colorectal Cancer Cells ◽

Sw620 Cells ◽

Cancer Tissues ◽

Dual Luciferase Reporter Assay

This work investigates the effect of circABCC4 on the proliferation, migration, and invasion of colorectal cancer SW620 cells; circABCC4’s regulation of miR-216a-3p is also studied. qRT-PCR was used to measure the levels of circABCC4 and miR-216a-3p in colorectal cancer and adjacent tissues. The human colorectal cancer SW620 cells were transfected with different constructs of circABCC4 or miR-216a-3p or both to study their interactions and combined effects on cell behavior. A dual-luciferase reporter experiment tested the targeted relationship between circABCC4 to miR-216a-3p. Furthermore, the behaviors of SW620 cells, such as cell viability, migration, and invasion, were investigated. Also, the proteins related to cell behaviors were investigated with western blotting. Our results showed that colorectal cancer tissues had a higher level of circABCC4 but a lower level miR-216a-3p. The increased level of circABCC4 and the reduced level of miR-216a-3p had analogous influences on the behaviors of SW620 cells, resulting in reduced cell proliferation, migration, and invasion; the levels of related protein were also decreased. Moreover, we found that disrupting miR-548c-3p could reverse the influence of inhibiting circABCC4 on SW620 cells. In addition, the dual-luciferase reporter assay results confirmed the targeting of miR-216a-3p by circABCC4. These data demonstrate that the silencing of circABCC4 may inhibit the proliferation, migration, and invasion of colorectal cancer cells by upregulating miR-548c-3p.

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miR-224 targets BTRC and promotes cell migration and invasion in colorectal cancer

3 Biotech ◽

10.1007/s13205-020-02477-x ◽

2020 ◽

Vol 10 (11) ◽

Author(s):

Qi Zheng ◽

Jane J. Yu ◽

Chenggang Li ◽

Jiali Li ◽

Jiping Wang ◽

...

Keyword(s):

Colorectal Cancer ◽

Cell Migration ◽

Protein Expression ◽

Molecular Mechanisms ◽

Early Stage ◽

Luciferase Assay ◽

Migration And Invasion ◽

Cell Migration And Invasion ◽

Normal Tissues ◽

The Impact

AbstractOur study aims to investigate the impact of miR-224 on cell migration and invasion in colorectal cancer (CRC) as well as its molecular mechanisms. The results showed that miR-224 was significantly upregulated in CRC compared to normal tissues via the TCGA database. Overexpression of miR-224 promoted CRC cell migration and invasion, while inhibition of miR-224 demonstrated the opposite result via transwell assays. In addition, we found that BTRC was a target gene of miR-224 through the miRecords database and dual-luciferase assay, while western blot together with RT-qPCR showed that inhibition of miR-224 led to elevated BTRC expression in protein level but not in mRNA level, and also decreased the expression of β-catenin. In reference to the Human Protein Atlas, BTRC protein expression was higher in normal tissues than in CRC tissues. In conclusion, miR-224 regulates its target BTRC protein expression and its related Wnt/β-catenin pathway. Its impact on cell migration and invasion in CRC cells suggested that miR-224 could be a prospective therapeutic target for early-stage non-metastatic CRC.

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Loss of the nuclear Wnt pathway effector TCF7L2 promotes migration and invasion of human colorectal cancer cells

Oncogene ◽

10.1038/s41388-020-1259-7 ◽

2020 ◽

Vol 39 (19) ◽

pp. 3893-3909 ◽

Cited By ~ 3

Author(s):

Janna Wenzel ◽

Katja Rose ◽

Elham Bavafaye Haghighi ◽

Constanze Lamprecht ◽

Gilles Rauen ◽

...

Keyword(s):

Colorectal Cancer ◽

Cancer Cells ◽

Wnt Pathway ◽

Migration And Invasion ◽

Human Colorectal Cancer ◽

Colorectal Cancer Cells ◽

Human Colorectal Cancer Cells

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DDX10 Promotes the Proliferation and Metastasis of Colorectal Cancer Cells via Splicing RPL35

10.21203/rs.3.rs-907936/v1 ◽

2021 ◽

Author(s):

Xin Zhou ◽

Zhihong Liu ◽

Cuifeng Zhang ◽

Manman Jiang ◽

Yuxiao Jin ◽

...

Keyword(s):

Colorectal Cancer ◽

Molecular Mechanisms ◽

Enrichment Analysis ◽

Gene Set Enrichment Analysis ◽

Migration And Invasion ◽

Ppi Network ◽

Interacting Protein ◽

Network Analyses ◽

Potential Biomarker

Abstract Background: Colorectal cancer (CRC) has become the second deadliest cancer in the world and severely threatens human health. An increasing number of studies have focused on the role of the RNA helicase DEAD-box (DDX) family in CRC. However, the mechanism of DDX10 in CRC has not been elucidated.Methods: In our study, we analysed the expression data of CRC samples from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. Subsequently, we performed cytological experiments and animal experiments to explore the role of DDX10 in CRC cells. Furthermore, we performed Gene Ontology (GO)/ Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and protein-protein interaction (PPI) network analyses. Finally, we predicted the interacting protein of DDX10 by LC-MS/MS and verified it by coimmunoprecipitation (Co-IP) and qPCR.Results: In the present study, we identified that DDX10 mRNA was extremely highly expressed in CRC tissues compared with normal colon tissues in the TCGA and GEO databases. The protein expression of DDX10 was measured by immunochemistry (IHC) in 17 CRC patients. The biological roles of DDX10 were explored via cell and molecular biology experiments in vitro and in vivo and cell cycle assays. We found that DDX10 knockdown markedly reduced CRC cell proliferation, migration and invasion. Then, we constructed a PPI network with the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING). GO and KEGG enrichment analysis and gene set enrichment analysis (GSEA) showed that DDX10 was closely related to RNA splicing and E2F targets. Using LC-MS/MS and Co-IP assays, we discovered that RPL35 is the interacting protein of DDX10. In addition, we hypothesize that RPL35 is related to the E2F pathway and the immune response in CRC.Conclusions: In conclusion, provides a better understanding of the molecular mechanisms of DDX10 in CRC and provides a potential biomarker for the diagnosis and treatment of CRC.

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Long non-coding RNA LINC00115 contributes to the progression of colorectal cancer by targeting miR-489-3p via PI3K/AKT/mTOR pathway

10.21203/rs.3.rs-45664/v1 ◽

2020 ◽

Author(s):

Weiyu Feng ◽

Baodong Li ◽

Jinbang Wang ◽

Huiliang Zhang ◽

Yonggang Liu ◽

...

Keyword(s):

Colorectal Cancer ◽

Molecular Mechanisms ◽

Biological Effects ◽

Inverse Correlation ◽

Mtor Signaling ◽

Cell Counting ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Regulatory Relationship ◽

Tissue Samples

Abstract Background Long noncoding RNAs (lncRNAs) are tumor-related regulators and have been found to be involved in the underlying molecular mechanisms of colorectal cancer (CRC). However, the role of lncRNA LINC00115 during CRC progression is not entirely elucidated. Methods The expression of LINC00115 was analyzed in paired CRC tissue samples and its clinical significance was evaluated. The biological effects on CRC cells proliferation, apoptosis, migration, invasion and PI3K/AKT/mTOR signaling were assessed by Cell Counting Kit-8 assay, Transwell assay, flow cytometry analysis and Western blot, respectively. The regulatory relationship between LINC00115 and miR-489-3p was determined by dual-luciferase reporter assays. Results LINC00115 was significantly overexpressed in CRC and its overexpression predicted poor outcome of the patients. Downregulation of LINC00115 markedly inhibited CRC cell proliferation, increased cell apoptosis, and suppressed cell migration and invasion. Moreover, downregulation of LINC00115 led to the inactivation of PI3K/AKT/mTOR signaling. Bioinformatics analysis identified miR-489-3p as a candidate target of LINC00115. Furthermore, we revealed an inverse correlation between LINC00115 and miR-489-3p in CRC tissues. miR-489-3p might directly target LINC00115 and downregulation of miR-489-3p could rescue the biological effects induced by the absence of LINC0015. Conclusion LINC00115 serves as an excellent oncogene of CRC metastasis, the deeper understanding of LINC00115/miR-489-3p axis might provide potential therapeutic targets for CRC metastasis.

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