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MicroRNA-183 Acts as a Tumor Suppressor in Human Non-Small Cell Lung Cancer by Down-Regulating MTA1
- Source :
- Cellular Physiology and Biochemistry, Vol 46, Iss 1, Pp 93-106 (2018)
- Publication Year :
- 2018
- Publisher :
- Cell Physiol Biochem Press GmbH & Co KG, 2018.
-
Abstract
- Backgrounds/Aims: MicroRNAs (miRs) often contribute to the progression of non-small cell lung cancer (NSCLC) via regulation of mRNAs that are involved in lung homeostasis. We conducted a study aimed at exploring the roles of miR-183 in the proliferation, epithelial-mesenchymal transition (EMT), invasion and migration of human NSCLC cells via targeting MTA1. Methods: NSCLC and adjacent normal tissues were collected from 194 patients with NSCLC. Positive expression of MTA1 protein was detected by immunohistochemistry. The highest levels of expression of miR-183 were detected using RT-qPCR in SPC-A-1 cells, which were selected and assigned to the following groups: blank, negative control (NC), miR-183 mimic, miR-183 inhibitor, siRNA-MTA1, and miR-183 inhibitor + siRNA-MTA1. The expression of miR-183 and the mRNA and protein expression of MTA1, E-cadherin, Vimentin, Snail, PCNA, Bax and Bcl-2 in tissues and transfected cells were measured using RT-qPCR and western blot analysis. Cell proliferation, apoptosis, migration and invasion were evaluated by CCK-8, flow cytometry, scratch tests and Transwell assays. Tumor xenografts were conducted in nude mice to determine tumor growth. Results: SPC-A-1 cells with the highest levels of miR-183 expression were selected. Compared with adjacent normal tissues, the expression of miR-183 and the mRNA and protein expression of E-cadherin and Bax were decreased in NSCLC tissues, while mRNA and protein expression of MTA1, Vimentin, snail, PCNA and Bcl-2 were increased. MiR-183 was over-expressed in the miR-183 mimic group and under-expressed in the miR-183 inhibitor and miR-183 inhibitor + siRNA-MTA1 groups. In the miR-183 mimic and siRNA-MTA1 groups, the mRNA and protein expression of E-cadherin and Bax, as well as cell apoptosis, were enhanced, while the expression levels of MTA1, Vimentin, snail, PCNA and Bcl-2 mRNA and protein, cell proliferation, migration, invasion and tumor growth were reduced relative to the blank and NC groups. The miR-183 inhibitor group exhibited an opposite trend. Conclusion: Our study indicates that miR-183 down-regulates MTA1 to inhibit the proliferation, EMT, migration and invasion of human NSCLC cells.
- Subjects :
- 0301 basic medicine
Lung Neoplasms
Physiology
MTA1 gene
Vimentin
lcsh:Physiology
Mice
0302 clinical medicine
Non-small cell lung cancer
Invasion
Cell Movement
Carcinoma, Non-Small-Cell Lung
lcsh:QD415-436
Migration
bcl-2-Associated X Protein
biology
medicine.diagnostic_test
lcsh:QP1-981
Transfection
Cadherins
Epithelial-mesenchymal transition
Proto-Oncogene Proteins c-bcl-2
030220 oncology & carcinogenesis
RNA Interference
Transplantation, Heterologous
Down-Regulation
Mice, Nude
Histone Deacetylases
Flow cytometry
lcsh:Biochemistry
03 medical and health sciences
Cell Line, Tumor
Proliferating Cell Nuclear Antigen
microRNA
medicine
Animals
Humans
Epithelial–mesenchymal transition
MicroRNA-183
Cell Proliferation
Cell growth
Antagomirs
Proliferating cell nuclear antigen
Repressor Proteins
MicroRNAs
030104 developmental biology
Apoptosis
biology.protein
Cancer research
Trans-Activators
Snail Family Transcription Factors
Subjects
Details
- Language :
- English
- ISSN :
- 14219778 and 10158987
- Volume :
- 46
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Cellular Physiology and Biochemistry
- Accession number :
- edsair.doi.dedup.....f70a55df701b8144da1f9ae9ce468b01