The effect of genetic variants of SLC22A18 on proliferation, migration, and invasion of colon cancer cells
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ABSTRACT:
SUBMITTER: Song H
PROVIDER: S-EPMC10873386 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
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Project description:BackgroundRho guanine nucleotide exchange factor 16 (ARHGEF16) is a newly discovered Rho-family guanine nucleotide exchange factor (GEF) involved in the activation of Rho-family GTPases. However, its roles in colon cancer cell proliferation, migration, and invasion remain unknown. This study analyzed the expression of ARHGEF16 in colon cancer and explored its biological effects on colon cancer cells, so as to find new therapeutic targets for the treatment of colon cancer.MethodsThe expression of ARHGEF16 in colon cancer tissues and cells was detected by bioinformatics analysis, western blot, and quantitative real time polymerase chain reaction (qRT-PCR) assays. The effects of overexpression and silencing of ARHGEF16 on the biological behavior of colon cancer cells were examined by Cell Counting Kit-8 (CCK-8), cell scratching and Transwell assays.ResultsThe database showed that ARHGEF16 was highly expressed in colon cancer tissues. Validation with clinical fresh tissue specimens and colon cancer cell lines revealed that ARHGEF16 was highly expressed in both. The proliferation, growth, migration, and invasion ability of colon cancer cell lines increased significantly with the overexpression of ARHGEF16, while silencing ARHGEF16 showed the opposite effect.ConclusionsThe expression of ARHGEF16 is closely related to the migration and invasive ability of colon cancer cells, and overexpression of ARHGEF16 promotes the migration and invasion of colon cancer cells and correlates with the metastatic potential of colon cancer.
| S-EPMC10774027 | biostudies-literature
Project description:BackgroundAccumulated studies indicate that aberrant expression of long noncoding RNAs (lncRNAs) is associated with tumorigenesis and progression of colon cancer. In the present study, long intergenic non-protein coding RNA 1287 (LINC01287) was identified to up-regulate in colon cancer by transcriptome RNA-sequencing, but the exact function remained unclear.MethodsTranscriptome RNA-sequencing was conducted to identify dysregulated lncRNAs. Expression of LINC01287 was evaluated by real-time quantitative PCR. The downstream targets of LINC01287 and miR-4500 were verified by luciferase reporter assay, pull down assay and western blot. The potential functions of LINC01287 were evaluated by cell viability assay, colony formation assay, soft agar assay, flow cytometry, transwell migration and invasion assay, and tumor xenograft growth in colon cancer cells.ResultsOur results indicated that LINC01287 was up-regulated in colon cancer patients. High LINC01287 expression was associated with advanced TNM stage, lymph node metastasis, distant metastasis and shorter overall survival. Knockdown of LINC01287 inhibited cell growth, colony formation in plates and soft agar, transwell cell migration and invasion, and epithelial-mesenchymal transition (EMT) of colon cancer cells, while LINC01287 overexpression had contrary effects. In addition, LINC01287 mediated MAP3K13 expression by sponging miR-4500, thus promoted NF-κB p65 phosphorylation. Restored MAP3K13 expression or miR-4500 knockdown partially abrogated the effects of silencing LINC01287 in colon cancer cells.ConclusionOur findings demonstrated that the LINC01287/miR-4500/MAP3K13 axis promoted progression of colon cancer. Therefore, LINC01287 might be a potential therapeutic target and prognostic marker for colon cancer patients.
| S-EPMC8259379 | biostudies-literature
Project description:Colon cancer is one of the most common cancer types. Its positive correlation with general obesity has led to increasing amounts of research focusing on the role of adipokines in colon cancer development. Apelin is a peptide released by adipose tissue that could affect many cellular processes connected with carcinogenesis. In this study, we examined the role of apelin in the motility regulation of colon cancer cells. We showed that the effect of four different apelin peptides increased the ability of cancer cells to migrate and invade examined cells trough influencing migratory protrusions formation and actin cytoskeleton rearrangement. Additionally, using confocal microscopy, we noticed that apelin stimulated the proteolytic activity of cancer cells, especially increasing the level of membrane-type 1 matrix metalloprotease. Taken together, apelin increased the movement of colon cancer cells through several possible mechanisms. Moreover, better understanding the process through which apelin regulates cancer development is still necessary to the creation of novel anti-cancer therapy.
| S-EPMC6115746 | biostudies-literature
Project description:Colon cancer is one of the major causes of cancer-related deaths worldwide. Long non-coding RNA (lncRNA) LINC01123 has been suggested to act as an oncogene in non-small cell lung cancer and a prognostic signature in head and neck squamous cell carcinoma. However, its role in colon cancer remains obscure. From TCGA database, LINC01123 was observed to be up-regulated in colon adenocarcinoma (COAD). Subsequently, the up-regulated LINC01123 was also detected in colon cancer cells. Functionally, LINC01123 could enhance cell proliferation, migration, invasion and angiogenesis. Moreover, the chemoresistance of colon cancer cells was verified to be promoted by LINC01123. Afterward, LINC01123 was found to bind with Ago2 and miR-34c-5p. Besides, miR-34c-5p was confirmed to inhibit the cellular process and chemoresistance of colon cancer cells. Then, VEGFA was disclosed to coexist with LINC01123 and miR-34c-5p in RNA-induced silencing complex. And TCGA database suggested that its expression was correlated with different stages of COAD. Moreover, it was uncovered that VEGFA could bind with miR-34c-5p and its expression positively correlated with LINC01123 expression. Finally, LINC01123 was proofed to regulate colon cancer progression and cells chemoresistance via VEGFA. In conclusion, LINC01123/miR-34c-5p/VEGFA axis promotes colon cancer malignancy and cells chemoresistance.
| S-EPMC7414518 | biostudies-literature
Project description:MicroRNA-423 (miR-423) is highly expressed in breast cancer (BC). Previously, our group showed that the SNP rs6505162:C>A located in the pre-miR-423 was significantly associated with increased familial BC risk in patients with a strong family history of BC. Therefore, in this study, we evaluated the functional role of rs6505162 in mammary tumorigenesis in vitro to corroborate the association of this SNP with BC risk. We found that rs6505162:C>A upregulated expression of both mature miR-423 sequences (3p and 5p). Moreover, pre-miR-423-A enhanced proliferation, and promoted cisplatin resistance in BC cell lines. We also showed that pre-miR-423-A expression decreased cisplatin-induced apoptosis, and increased BC cell migration and invasion. We propose that the rs6505162-A allele promotes miR-423 overexpression, and that the rs6505162-A allele induces BC cell proliferation, viability, chemoresistance, migration, and invasion, and decreases cell apoptosis as a consequence. We suggest that rs6505162:C>A is a functional SNP site with potential utility as a marker for early diagnosis, prognosis, and treatment efficacy monitoring in BRCA1/2-negative BC patients, as well as a possible therapeutic target.
| S-EPMC8745459 | biostudies-literature
Project description:BACKGROUND Prostate cancer (PCa), accounting for 28% of all male cancer cases, is the second leading cause of cancer-related death among men. NFATc1, belonging to the NFAT family, is overexpressed in PCa and is correlated with the risk of recurrence after radical prostatectomy. MATERIAL AND METHODS In the present study, the expression of NFATc, c-myc, and PKM2 in PCa cells was regulated by lentiviruses and then detected by real-time PCR and Western blot analysis. Further, proliferation, invasion, and migration assays were performed. The glucose consumption and lactate production were assessed by biochemical detection. RESULTS We found that NFATc1 down-regulation significantly suppressed the proliferation and Warburg effect of PCa cells, concurrent with a decrease of c-myc and PKM2 expression. Likewise, the abilities of migration and invasion were also inhibited in NFATc1-silenced PCa cells. In addition, NFATc1 down-regulation-induced inhibition of cell proliferation, migration, invasion, and Warburg effect were counteracted by up-regulation of c-myc or PKM2. The expression of PKM2 was positively regulated by NFATc1 and c-myc expression. CONCLUSIONS These results indicate that NFATc1 down-regulation can suppress the proliferation, Warburg effect, and migration and invasion abilities of PCa cells, probably by regulating c-myc and PKM2 expression. NFATc1 may be a potential therapeutic target for PCa and could be used as a diagnosis or prognosis indicator of PCa.
| S-EPMC6404685 | biostudies-literature
Project description:Transient receptor potential vanilloid 2 (TRPV2), a nonselective cation channel, has become an attractive target gene for tumor studies due to its wide range of physiological and pathological functions. However, its specific role in bladder cancer development and progression remains unclear. The aim of the present study was to investigate the effects of TRPV2 on the proliferation, migration and invasion of 5637 bladder cancer cells in vitro. Rat TRPV2 cDNA was transfected into 5637 bladder cancer cells and changes in the behavior of the cells were detected. It was observed that TRPV2 enhanced bladder cancer cell migration and invasion; however, it did not affect cell proliferation in vitro. TRPV2 activity, which may be mediated by direct matrix metalloproteinase 2 (MMP2) regulation, is important in bladder tumor development and progression. The results of this study suggest that TRPV2 channels are a potential therapeutic target for bladder carcinoma.
| S-EPMC3820795 | biostudies-literature
Project description:This study aimed to explore the effects of CLIC1 gene silencing on proliferation, migration, invasion and apoptosis of human gallbladder cancer (GBC). GBC and normal gallbladder tissues were extracted for the detection of mRNA and protein expressions of CLIC1. GBC-SD and NOZ cells in the logarithmic growth phase were selected to conduct the experiment. Three different siRNA recombined expression vectors were established using CLIC1 as a target at different sites. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blotting were, respectively, used to detect the CLIC1 mRNA and protein expressions. MTT assay was performed to detect the cell proliferation. Flow cytometry was applied to measure the cell apoptosis and cell cycle distribution. The variations of cell migration and invasion were evaluated using Transwell assay. GBC tissues showed higher CLIC1 mRNA and protein expressions than normal gallbladder tissues. The CLIC1 mRNA and protein expressions in the CLIC1 siRNA group were significantly lower than those in the NC and blank groups. Compared with the NC and blank groups, the CLIC1 siRNA group showed a significant decrease in cell proliferation but an obvious increase in apoptosis rate in GBC cells. Besides, in the CLIC1 siRNA group, cell percentage in G0/G1 and G2/M phase was gradually increased but decreased in S phases. The migration and invasion abilities in GBC cells were significantly lower than those in the NC and blank groups. Our study demonstrates that CLIC1 gene silencing could promote apoptosis and inhibit proliferation migration and invasion of GBC cells.
| S-EPMC5908121 | biostudies-literature
Project description:Double homeobox A pseudogene 8 (DUXAP8) is a known tumor promoter in several malignancies. Nonetheless, its function in colon cancer (CC) is indefinite. Herein, we explored the significance of DUXAP8 and its underlying mechanism in CC. Our data indicated that DUXAP8 was upregulated in CC, and it was related to advanced stages and lymph node metastases. Based on our Kaplan-Meier survival analysis, elevated DUXAP8 expression resulted in shorter patient overall survival (OS). Conversely, DUXAP8 silencing strongly suppressed cellular proliferation, migration and invasion in vitro. Based on our western blot analysis, DUXAP8 deficiency strongly inhibited the epithelial-mesenchymal transition (EMT) in vitro. Alternately, DUXAP8 overexpression accelerated cellular proliferation migration and invasion in CC. Finally, silencing DUXAP8 prevented tumorigenesis in a mouse xenograft model in vivo. Collectively, our results demonstrated that DUXAP8 regulates the occurrence and advancement of CC, and may serve as a regulatory hub for this disease.
| S-EPMC9161926 | biostudies-literature
Project description:Caspase-3 (CASP3) is a major mediator of apoptosis activated during cellular exposure to cytotoxic drugs, radiotherapy or immunotherapy. It is often used as a marker for efficacy of cancer therapy. However, recent reports indicate that caspase-3 has also non-apoptotic roles such as promotion of tumor relapse and tumor angiogenesis. Therefore, the roles of caspase-3 in tumor progression remain to be defined clearly. In our study, we established caspase-3 knockout (KO) colon cancer cell lines by use of the CRISPR technology. In vitro, caspase-3 knockout HCT116 cells were significantly less clonogenic in soft agar assays. They were also significantly less invasive and more sensitive to radiation and mitomycin C than control cells. In vivo, CASP3KO cells formed tumors at rates similar to control cells but were significantly more sensitive to radiotherapy. They were also less prone to pulmonary metastasis when inoculated either subcutaneously or intravenously. At the mechanistic level, caspase-3 gene knockout appeared to cause reduced EMT phenotypes when compared to parental HCT116 cells. Indeed, they showed significantly increased E-cadherin expression, reduced N-cadherin, Snail, Slug and ZEB1 expression than control cells. Therefore, therapeutic targeting of caspase-3 may not only increase the sensitivity of cancer cell to chemotherapy and radiotherapy, but also inhibit cancer cell invasion and metastasis.
| S-EPMC6204286 | biostudies-literature