Abstract 2440: The microRNA-mRNA interactions inALK-rearranged lung adenocarcinoma

Background: ALK-rearranged lung adenocarcinoma, which is responsive to ALK inhibitors, exhibits distinct clinicopathological and molecular features. In ALK-rearranged lung cancer, miRNA/mRNA expression signatures or individual miRNA-mRNA interactions have been reported. However, no study has performed integrative analysis to identify comprehensive miRNA-mRNA interactive network in this type of tumor. Therefore, we conducted this study to reveal a landscape of miRNA-mRNA interactions present in ALK-rearranged lung adenocarcinoma. Methods: To identify differentially expressed miRNAs and mRNAs according to ALK-rearranged status, microarray expression profiling was conducted using 77 surgically resected specimens of lung adenocarcinoma with a known ALK status (42 ALK-positive and 35 ALK-negative cases). We made a multistep bioinformatics approach to build an miRNA-mRNA regulatory network observed in ALK-rearranged lung tumors. Results: Seventy-three miRNAs (comprising 56 downregulated and 17 upregulated miRNAs) were differentially expressed according to ALK-rearranged status. The 56 miRNAs included miR-19a-3p, miR-362-5p, and miR-340-5p, all of which have been reported to be downregulated in ALK-rearranged lung tumors. On the basis of miRNA expression data, we identified 80 distinct biological processes in ALK-positive tumors, which included “proteoglycans in cancer”, “FoxO signaling pathway”, “pathways in cancer”, “mTOR signaling pathway”, and “HIF-1 signaling pathway”. The mRNA expression signature of ALK-rearranged tumors included ALK, ETV1, and CX3CL1, all of which have been associated with lung tumorigenesis or tumor progression. Integrative analyses of miRNA and mRNA expression data revealed a refined list of putative miRNA-mRNA correlations. Of 136 putative miRNA-mRNA interactions, we identified 101 distinctive interactions with potential involvement in oncogenic machinery in ALK-positive tumors, such as miR-19a-3p/TLR2, miR-362-5p/SLC34A2, miR-1260b/ETV1, and miR-4481/CX3CL1 pairs. Network structural analysis provided a comprehensive view of complex miRNA-mRNA interactions in ALK-rearranged lung adenocarcinoma. Conclusion: Overall, this observational study provides insight into the unique miRNA-mRNA regulatory network present in ALK-rearranged lung adenocarcinoma. Our findings, if validated, would inform future research examining the interplay of miRNAs and mRNAs in ALK-rearranged tumors. Citation Format: Sophia Subat, Kentaro Inamura, Hironori Ninomiya, Hiroko Nagano, Sakae Okumura, Yuichi Ishikawa. The microRNA-mRNA interactions in ALK-rearranged lung adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2440.