Integrative analysis of negatively regulated miRNA-mRNA axes for esophageal squamous cell carcinoma

Article type: Research Article

Authors: Peng, Shuang^{a; 1} | Zhang, Shiyu^{a; 1} | Fan, Xingchen^{b; 1} | Zhu, Jingfeng^c | Liu, Cheng^d | Yue, Yulin^{e; *} | Wang, Tongshan^{a; *} | Zhu, Wei^{a; *}

Affiliations: [a] Department of Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China | [b] Department of Geriatrics, The First People’s Hospital of Lianyungang, Lianyungang, Jiangsu, China | [c] Department of Nephrology, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China | [d] Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China | [e] Department of Laboratory, Children’s Hospital of Nanjing Medical University, Nanjing, Jiangsu, China

Correspondence: [*] Corresponding authors: Wei Zhu, Department of Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China. Tel.: +86 139 13894911, E-mail: zhuwei@njmu.edu.cn. Tongshan Wang, Department of Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China. Tel.: +86 137 05174300, E-mail: wangtongshan@jsph.org.cn. Yulin Yue, Department of Laboratory, Children’s Hospital of Nanjing Medical University, Nanjing, Jiangsu, China. Tel.: +86 177 88388125, E-mail: yueyulin@njmu.edu.cn.

Note: [1] Shuang Peng, Shiyu Zhang, and Xingchen Fan have contributed equally to this work.

Abstract: BACKGROUND: MicroRNAs regulating mRNA expression by targeting at mRNAs is known constructive in tumor occurrence, immune escape, and metastasis. OBJECTIVE: This research aims at finding negatively regulatory miRNA-mRNA pairs in esophageal squamous cell carcinoma (ESCC). METHODS: GENE expression data of The Cancer Genome Atlas (TCGA) and GEO database were employed in differently expressed RNA and miRNA (DE-miRNAs/DE-mRNAs) screening. Function analysis was conducted with DAVID-mirPath. MiRNA-mRNA axes were identified by MiRTarBase and TarBase and verified in esophageal specimen by real-time reverse transcription polymerase chain reaction (RT-qPCR). Receiver operation characteristic (ROC) curve and Decision Curve Analysis (DCA) were applied in miRNA-mRNA pairs predictive value estimation. Interactions between miRNA-mRNA regulatory pairs and immune features were analyzed using CIBERSORT. RESULTS: Combining TCGA database, 4 miRNA and 10 mRNA GEO datasets, totally 26 DE-miRNAs (13 up and 13 down) and 114 DE-mRNAs (64 up and 50 down) were considered significant. MiRTarBase and TarBase identified 37 reverse regulation miRNA-mRNA pairs, 14 of which had been observed in esophageal tissue or cell line. Through analysis of RT-qPCR outcome, miR-106b-5p/KIAA0232 signature was chosen as characteristic pair of ESCC. ROC and DCA verified the predictive value of model containing miRNA-mRNA axis in ESCC. Via affecting mast cells, miR-106b-5p/KIAA0232 may contribute to tumor microenvironment. CONCLUSIONS: The diagnostic model of miRNA-mRNA pair in ESCC was established. Their complex role in ESCC pathogenesis especially tumor immunity was partly disclosed.

Keywords: Biomarkers, miRNA-mRNA interaction, esophageal squamous cell carcinoma, TCGA, GEO, PCR

DOI: 10.3233/CBM-220309

Journal: Cancer Biomarkers, vol. 37, no. 3, pp. 191-203, 2023