miR-7112-3p targets PERK to regulate the endoplasmic reticulum stress pathway and apoptosis induced by photodynamic therapy in colorectal cancer CX-1 cells

• Published in: Photodiagnosis and photodynamic therapy 2020-03, Vol.29, p.101663-101663, Article 101663
• Main Authors: Kong, Fanhua, Zou, Heng, Liu, Xi, He, Jun, Zheng, Yanwen, Xiong, Li, Miao, Xiongying
• Format: Article
• Language: English
• Subjects: Apoptosis; Apoptosis - drug effects; Cell Line, Tumor; Cell Survival - drug effects; Colorectal cancer; Colorectal Neoplasms - drug therapy; eIF-2 Kinase - metabolism; Endoplasmic reticulum stress; Endoplasmic Reticulum Stress - drug effects; Humans; MicroRNAs - physiology; miR-7112-3p; PERK; Photochemotherapy - methods; Photodynamic therapy; Photosensitizing Agents - chemistry; Photosensitizing Agents - pharmacology; Porphyrins - chemistry; Porphyrins - pharmacology; Signal Transduction - drug effects
• ISSN: 1572-1000; 1873-1597
• DOI: 10.1016/j.pdpdt.2020.101663

•MiR-7112-3p is highly expressed in colorectal cancer tissue, which directly targets PERK in CX-1 cells.•Endoplasmic reticulum is involved in the subcellular accumulation of DVDMS in CX-1 cells.•Depressed expression of miR-7112-3p alleviated the inhibition of PERK and induced apoptosis by DVDMS-PDT. Colorectal cancer (CRC) is the third most common malignant tumor worldwide. Photodynamic therapy (PDT) is an emerging modality for the treatment of solid tumors. Sinoporphyrin sodium (DVDMS) is a new photosensitizer with good therapeutic killing effects on cancer cells. Recent findings have shown that microRNAs play important roles in many biological processes. However, the functions of microRNAs in DVDMS-induced PDT remain largely unclear. Proteins involved in endoplasmic reticulum (ER) stress and apoptosis of CX-1 cells treated with DVDMS-PDT were examined by Western blotting and cell viability assays. 15 candidate miRNAs targeting RNA-dependent protein kinase-like ER kinase (PERK) were screened and verified using the TargetScan, miRWalk and miRDB databases. The downstream pathways of candidate miRNAs with high scores were studied by cell transfection, qRT-PCR, Western blotting and dual-luciferase reporter assays. The subcellular location of DVDMS was confirmed by laser confocal microscopy. DVDMS-PDT induced apoptosis via elevated ER stress and activation of the PERK/ATF4/CHOP/caspase cascade pathway in CX-1 cells. The endoplasmic reticulum was involved in the subcellular accumulation of DVDMS in CX-1 cells. Dual-luciferase reporting experiment confirmed that a direct crosslinking between miR-7112-3p and PERK. In addition, miR-7112-3p was highly expressed in CRC tissues compared with peripheral tissues. Our work showed that miR-7112-3p directly targeted PERK and further regulated PERK/ATF4/CHOP/caspase cascade pathway, resulting in enhanced apoptosis in CX-1 cells treated with DVDMS-PDT.