HISTOLOGY AND HISTOPATHOLOGY

From Cell Biology to Tissue Engineering

 

Down-regulated REIC expression in lung carcinogenesis: a molecular target for gene therapy

Lei Yang, Shuang Zhao, Pu Xia and Hua-chuan Zheng

Department of Experimental Oncology, Shengjing Hospital of China Medical University, Shenyang, China

Offprint requests to: Hua-chuan Zheng, Department of Experimental Oncology, Shengjing Hospital of China Medical University, Shenyang 110004, China. e-mail: zheng_huachuan@hotmail.com


Summary. REIC (Reduced Expression in Immortalized Cells) gene is down-regulated in immortalized cells, compared with the normal parental counterparts. Its encoding protein could inhibit colony formation, tumor growth, and induce apoptosis. To investigate the roles of REIC expression in lung cancer, we examined REIC expression in lung cancer cells and tissues by RT-PCR or Western blot, and observed the effects of both recombinant REIC exposure and REIC overexpression on the aggressive phenotypes of lung cancer cells. It was found that the demethylation of REIC promoter by 5-Aza-dC could reserve its mRNA expression in lung cancer cells (P<0.05). There was a lower REIC mRNA expression in lung cancer than that in matched normal tissue (P<0.05). Recombinant REIC treatment enhanced the proliferation of lung cancer cells (P<0.05), but versa for REIC overexpression (P<0.05). Both recombinant REIC treatment and REIC overexpression induced apoptosis, and inhibited the migration and invasion of SQ-5 and KJ cells (P<0.05). Immunohistochemically, there was a positive correlation between REIC and Caspase-3 expression in lung cancer (P<0.05). According to Kaplan-Meier plotter, REIC mRNA overexpression was found to positively correlate with overall, progression-free and post- progression survival rates of lung cancer patients (P<0.05), even stratified by sex, histological subtyping, grading, TNM staging, chemotherapy, radiotherapy, or smoking. These findings suggested that down-regulated REIC expression might be involved in lung carcinogenesis due to its promoter methylation. Both recombinant REIC exposure and REIC overexpression might reverse the aggressive phenotypes of lung cancer cells. REIC may be employed as a potential target of gene therapy for lung cancer. Histol Histopathol 33, 691-704 (2018)

Key words: REIC, Lung cancer, Carcinogenesis, Phenotypes, Prognosis

DOI: 10.14670/HH-11-964