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CNOT4 suppresses non-small cell lung cancer progression and is required for effector cytolytic T lymphocytes cell responses to lung cancer cells
- Source :
- Molecular Immunology. 132:165-171
- Publication Year :
- 2021
- Publisher :
- Elsevier BV, 2021.
-
Abstract
- The therapeutic options of non-small cell lung cancer (NSCLC) are limited, although a combination of targeted therapy and immunotherapy is promising. To explore novel targets for immunotherapy, we explored the role of Ccr4-Not transcription complex subunit 4 (CNOT4) in NSCLC. The expression of CNOT4 in tumor tissues was determined by immunohistochemistry staining and western blotting. The cell lines that stably express CNOT4 were established in H1299 and A549 cells. Direct cell counting, MTT assay, and colony formation were used to determine the ability of cell proliferation. Cell apoptosis and cell cycle were next analyzed by PI/Annexin V staining. Cell invasion and migration were examined by transwell assays. To further explore the function of CNOT4 in cytotoxic T lymphocytes (CTLs) mediated cytotoxicity, an in vitro co-culture system of CNOT4 overexpressing and control H1299 cells with CTLs was developed. CNOT4 was down-regulated in tumor tissues compared with paired normal tissues from patients with lung cancers. CNOT4 overexpression significantly inhibited tumor cell proliferation, colony formation, cell migration, and invasion, but promoted cell apoptosis. Furthermore, overexpression of CNOT4 enhanced cytotoxicity of CTLs to H1299. CNOT4 functions as a potential tumor suppressor of NSCLC via inhibiting tumor cell function and increasing the sensitivity to CTLs.
- Subjects :
- 0301 basic medicine
Lung Neoplasms
medicine.medical_treatment
Immunology
Cell
Down-Regulation
Apoptosis
03 medical and health sciences
0302 clinical medicine
Cell Movement
Carcinoma, Non-Small-Cell Lung
Cell Line, Tumor
medicine
Humans
Cytotoxic T cell
Cytotoxicity
Molecular Biology
Cell Proliferation
A549 cell
Cell growth
Chemistry
Cell Cycle
Cell migration
Immunotherapy
Cell cycle
MicroRNAs
030104 developmental biology
medicine.anatomical_structure
A549 Cells
Cancer research
T-Lymphocytes, Cytotoxic
Transcription Factors
030215 immunology
Subjects
Details
- ISSN :
- 01615890
- Volume :
- 132
- Database :
- OpenAIRE
- Journal :
- Molecular Immunology
- Accession number :
- edsair.doi.dedup.....80a28a468424e37c1d23d74caa5b1b50