ArticleNeoplasia (New York, N.Y.)2017
Specific microRNA-mRNA Regulatory Network of Colon Cancer Invasion Mediated by Tissue Kallikrein-Related Peptidase 6.
Article in Neoplasia (New York, N.Y.), 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 32 citations in OpenAlex.
- A bioinformatics analysis of the target role of miRNA-431-5p on KLK6 in colorectal cancer.Hereditas · 2025Article
- Kallikrein-Related Peptidase 6 Contributes to Murine Intestinal Tumorigenesis Driven by a MutantCancers · 2024Article
- SOX2 inhibits LLGL2 polarity protein in esophageal squamous cell carcinoma via miRNA-142-3p.Cancer biology & therapy · 2022Article
- A KLK6 Activity-Based Probe Reveals a Role for KLK6 Activity in Pancreatic Cancer Cell Invasion.Journal of the American Chemical Society · 2022Article
- TGF-β Signaling in Metastatic Colorectal Cancer (mCRC): From Underlying Mechanism to Potential Applications in Clinical Development.International journal of molecular sciences · 2022Review
- Promotion or remission: a role of noncoding RNAs in colorectal cancer resistance to anti-EGFR therapy.Cell communication and signaling : CCS · 2022Review
- Scalable synthesis and structural characterization of reversible KLK6 inhibitors.RSC advances · 2022Article
- Kallikrein-Related Peptidase 6 (KLK6) as a Contributor toward an Aggressive Cancer Cell Phenotype: A Potential Role in Colon Cancer Peritoneal Metastasis.Biomolecules · 2022Article
- KLK6 mediates stemness and metabolism of gastric carcinoma cells via the PI3K/AKT/mTOR signaling pathway.Oncology letters · 2021Article
- KLK8 promotes the proliferation and metastasis of colorectal cancer via the activation of EMT associated with PAR1.Cell death & disease · 2021Article
- Noncoding RNAs as Promising Diagnostic Biomarkers and Therapeutic Targets in Intestinal Fibrosis of Crohn's Disease: The Path From Bench to Bedside.Inflammatory bowel diseases · 2021Review
- Article
- Synthesis and Structure-Activity Relationships of N-(4-Benzamidino)-Oxazolidinones: Potent and Selective Inhibitors of Kallikrein-Related Peptidase 6.ChemMedChem · 2020Article
- Kallikrein 6 protease advances colon tumorigenesisOncotarget · 2019Article
- Article
- Identification of a miRNA-mRNA network associated with lymph node metastasis in colorectal cancer.Oncology letters · 2019Article
- Differential Connectivity in Colorectal Cancer Gene Expression NetworkIranian biomedical journal · 2019Article
- Small RNA sequencing of sessile serrated polyps identifies microRNA profile associated with colon cancer.Genes, chromosomes & cancer · 2019Article
- The TGFβ-signaling pathway and colorectal cancer: associations between dysregulated genes and miRNAs.Journal of translational medicine · 2018Article
- Network-based analysis of oligodendrogliomas predicts novel cancer gene candidates within the region of the 1p/19q co-deletion.Acta neuropathologica communications · 2018Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Metastatic colon cancer is a major cause of deaths among colorectal cancer (CRC) patients. Elevated expression of kallikrein 6 (KLK6), a member of a kallikrein subfamily of peptidase S1 family serine proteases, has been reported in CRC and is associated with low patient survival rates and poor disease prognosis. We knocked down KLK6 expression in HCT116 colon cancer cells to determine the significance of KLK6 expression for metastatic dissemination and to identify the KLK6-associated microRNAs (miRNAs) signaling networks in metastatic colon cancer. KLK6 suppression resulted in decreased cells invasion in vitro with a minimal effect on the cell growth and viability. In vivo, animals with orthotopic colon tumors deficient in KLK6 expression had the statistically significant increase in survival rates (P=.005) and decrease in incidence of distant metastases. We further performed the integrated miRNA and messenger RNA (mRNA) expression profiling to identify functional miRNA-mRNA interactions associated with KLK6-mediated invasiveness of colon cancer. Through bioinformatics analysis we identified and functionally validated the top two up-regulated miRNAs, miR-182 and miR-203, and one down-regulated miRNA, miRNA-181d, and their seven mRNA effectors. The established miRNA-mRNA interactions modulate cellular proliferation, differentiation and epithelial-mesenchymal transition (EMT) in KLK6-expressing colon cancer cells via the TGF-β signaling pathway and RAS-related GTP-binding proteins. We confirmed the potential tumor suppressive properties of miR-181d and miR-203 in KLK6-expressing HCT116 cells using Matrigel invasion assay. Our data provide experimental evidence that KLK6 controls metastasis formation in colon cancer via specific downstream network of miRNA-mRNA effectors.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.