Expressions of miR-302a, miR-105, and miR-888 Play Critical Roles in Pathogenesis, Radiotherapy, and Prognosis on Rectal Cancer Patients: A Study From Rectal Cancer Patients in a Swedish Rectal Cancer Trial of Preoperative Radiotherapy to Big Database Analyses.

Autor:	Meng WJ; Department of Oncology and Department of Biomedical and Clinical Sciences, University of Linköping, Linköping, Sweden.; Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China., Pathak S; Department of Oncology and Department of Biomedical and Clinical Sciences, University of Linköping, Linköping, Sweden.; Chettinad Hospital & Research Institute, Chettinad Academy of Research and Education, Kelambakkam, India., Zhang X; School of Medicine, Institute of Medical Sciences, Örebro University, Örebro, Sweden., Adell G; County Council of Östergötland, University of Linköping, Linköping, Sweden., Jarlsfelt I; Department of Pathology, Ryhov Hospital, Jönköping, Sweden., Holmlund B; Department of Oncology and Department of Biomedical and Clinical Sciences, University of Linköping, Linköping, Sweden., Wang ZQ; Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China., Zhang AS; Department of Oncology-Pathology, Karolinska Institute, Stockholm, Sweden., Zhang H; School of Medicine, Institute of Medical Sciences, Örebro University, Örebro, Sweden., Zhou ZG; Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China.; State Key Laboratory of Biotherapy and Cancer Center, Institute of Digestive Surgery, West China Hospital, Sichuan University, Chengdu, China., Sun XF; Department of Oncology and Department of Biomedical and Clinical Sciences, University of Linköping, Linköping, Sweden.
Jazyk:	angličtina
Zdroj:	Frontiers in oncology [Front Oncol] 2020 Oct 06; Vol. 10, pp. 567042. Date of Electronic Publication: 2020 Oct 06 (Print Publication: 2020).
DOI:	10.3389/fonc.2020.567042
Abstrakt:	Differential expressions and functions of various micoRNAs (miRNAs) have been intensively studied in both colon and rectal cancers. However, the importance of miRNAs on radiotherapy (RT) response and clinical outcome in rectal cancer patients remains unclear. In this study, we used real-time polymerase chain reaction to examine the expressions of miR-302a, miR-105, and miR-888 in normal mucosa and cancer tissue from rectal cancer patients with and without preoperative RT. The biological function of miR-302a, miR-105, and miR-888 expression was further analyzed and identified through the public databases: TCGA (The Cancer Genome Atlas) and GEPIA (Gene Expression Profiling Interactive Analysis). The results showed that the expression of miR-105 in rectal cancer was higher than that in normal mucosa in RT ( P = 0.042) and non-RT patients ( P = 0.003) and was associated with mucinous histological type ( P = 0.004), COX-2 ( P = 0.042), and p73 expression ( P = 0.030). The expression of miR-302a was shown more frequently in cancers with necrosis ( P = 0.033) and with WRAP53 expression ( P = 0.015), whereas miR-888 expression occurred more frequently in tumors with protein the expression of survivin ( P = 0.015), AEG-1 (astrocyte elevated gene-1) ( P = 0.003), and SATB1 (special AT-rich sequence binding protein 1) ( P = 0.036). Moreover, TargetScan also predicted AEG-1 and SATB1 as putative targets for miR-888. The miRNA-gene network analysis showed that ABI2 was associated with all the three miRNAs, with lower expression and good diagnostic value in rectal cancers. The TCGA database demonstrated the association of miR-105 expression with high carcinoembryonic antigen level ( P = 0.048). RT reduced the expressions of miR-302a, miR-105, and miR-888. Prognostic analysis showed that miR-888 expression was independently associated with worse survival of patients without RT [overall survival, P = 0.001; disease-free survival, P = 0.009]. Analysis of biological function revealed that the protein serine/threonine kinase activity and PI3K-AKT signaling pathway were the most significantly enriched functions and pathways, respectively. Our findings suggest that miR-105 is involved in rectal cancer pathogenesis and miR-888 is associated with prognosis. MiR-302a, miR-105, and miR-888 have potential influence on the pathogenesis, RT, and prognosis of rectal cancer. (Copyright © 2020 Meng, Pathak, Zhang, Adell, Jarlsfelt, Holmlund, Wang, Zhang, Zhang, Zhou and Sun.)
Databáze:	MEDLINE
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