STRESS granule-associated RNA-binding protein CAPRIN1 drives cancer progression and regulates treatment response in nasopharyngeal carcinoma.
Te YangLong HuangHaide QinShijuan MaiPublished in: Medical oncology (Northwood, London, England) (2022)
Nasopharyngeal carcinoma (NPC) is a common malignancy of the head and neck that is mainly diagnosed in southern China and Southeast Asia, with a strong etiological link to Epstein‒Barr virus infection. Those with advanced-stage disease have a significantly worse prognosis. There is an urgent need to identify novel therapeutic targets for the recurrent or metastatic nasopharyngeal carcinoma. With a particular focus on Cell Cycle Associated Protein 1 (CAPRIN1), one of the important RNA-binding proteints associated with stress granule formation, we used RT‒qPCR and immunohistochemistry to validate CAPRIN1 expression in NPC tissues and cell lines. Further, CAPRIN1 expression was knocked down using siRNA, and the effect on cell proliferation and migration was systematically assessed by in vitro assays. As a result, we demonstrated that CAPRIN1 was elevated in NPC compared to adjacent normal tissues. Knockdown of CAPRIN1 in NPC cells inhibited proliferation and migration, involving the regulation of cell cycle protein CCND2 and EMT signaling, respectively. Notably, we found that CAPRIN1 knockdown promoted cell apoptosis by regulation of the expression of apoptosis-related proteins cleaved-PARP and cleaved-Caspase3. Knockdown of CAPRIN1 increased NPC cell sensitivity to rapamycin, and increased NPC cell sensitivity to cisplatin and to X-rays. In conclusion, CAPRIN1 might drive NPC proliferation, regulate cell cycle and apoptosis, and affect tumor cell response to anti-cancer agents and X-ray irradiation. CAPRIN1 might serve as a potential target for NPC.
Keyphrases
- cell cycle
- cell proliferation
- binding protein
- single cell
- epstein barr virus
- poor prognosis
- cell therapy
- cell cycle arrest
- cell death
- induced apoptosis
- oxidative stress
- endoplasmic reticulum stress
- squamous cell carcinoma
- signaling pathway
- epithelial mesenchymal transition
- dna damage
- magnetic resonance imaging
- diffuse large b cell lymphoma
- radiation therapy
- magnetic resonance
- mass spectrometry
- small molecule
- long non coding rna
- climate change
- dna repair
- bone marrow
- mesenchymal stem cells
- stress induced
- nucleic acid