Collagen triple helix repeat containing-1 negatively regulated by microRNA-30c promotes cell proliferation and metastasis and indicates poor prognosis in breast cancer
| Autor: | Xiao-hong Lin, Jian Chen, Xiao-ping Wang, Yuan-Hui Lai, Hai-Tao Peng, Wen-jian Wang, Yan-Qing Wu |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Cancer Research Pathology Apoptosis Metastasis 0302 clinical medicine Breast cancer Cell Movement Odds Ratio Neoplasm Metastasis Extracellular Matrix Proteins Cell migration Middle Aged lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens Prognosis Immunohistochemistry Tumor Burden Oncology 030220 oncology & carcinogenesis miR-30c Female RNA Interference Signal Transduction Adult medicine.medical_specialty Cell type Breast Neoplasms lcsh:RC254-282 03 medical and health sciences Cell Line Tumor microRNA medicine Biomarkers Tumor Humans Viability assay Aged Cell Proliferation Neoplasm Staging Cell growth business.industry Research medicine.disease MicroRNAs 030104 developmental biology Cancer cell Cancer research Neoplasm Grading business Biomarkers CTHRC1 |
| Zdroj: | Journal of Experimental & Clinical Cancer Research : CR Journal of Experimental & Clinical Cancer Research, Vol 36, Iss 1, Pp 1-15 (2017) |
| ISSN: | 1756-9966 0392-9078 |
| Popis: | Background Collagen triple helix repeat containing-1 (CTHRC1), which was firstly identified overexpressed in the adventitia and neointima of injured rat arteries, could inhibit collagen expression and increase cell migration. It was then found to be ubiquitously expressed in numerous cell types such as fibroblasts and smooth muscle cells, and aberrantly up-regulated in several malignant tumors. However, the functional role of CTHRC1 and its related mechanism in breast cancer still remains unclear. Methods CTHRC1 expressions in breast cancer tissues and cells were assessed by qRT-PCR, western blot and immunohistochemistry. The relative expression level of miR-134, miR-155, miR-30c and miR-630 in breast cancer cells respectively was detected by qRT-PCR. Wild type (Wt) and Mutant type (Mut) CTHRC1 3’UTR sequences were cloned into a psi-CHECK2 reporter vector, and the relative luciferase activity was detected by dual-luciferase reporter assay in indicated cells. The effect of ectopic expression of miR-30c or gain and loss of CTHRC1 on cell viability, cell proliferation, cell cycle progression and apoptosis, cell invasion and migration was respectively detected by CCK-8 assay, colony formation assay, flow cytometry analysis, transwell invasion/migration assay. Protein levels of β-catenin, active β-catenin, normal and phosphorylated form of GSK-3β were detected by western blot in indicated cells. Immunofluorescence staining of β-catenin was performed to observe nuclear localization. Results We found CTHRC1 was frequently up-regulated in human breast cancer cells and tissues. Then our cohort study and further meta-analysis validated high expression of CTHRC1 was associated with aggressive clinicopathological features and poor clinical outcome of breast cancer patients. In addition, CTHRC1 promoted cell proliferation, invasion and migration and suppressed cell apoptosis in breast cancer, which might be by activating GSK-3β/β-catenin signaling and inhibiting Bax/Caspase-9/Caspase-3 signaling respectively; and these biological functions of CTHRC1 could be directly negatively regulated by miR-30c. Conclusion Taken together, we identified the role of miR-30c/CTHRC1 axis in breast cancer progression and demonstrated CTHRC1 may serve as a prognostic biomarker and therapeutic target for breast cancer. Electronic supplementary material The online version of this article (doi:10.1186/s13046-017-0564-7) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
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