Abstract LB270: LINGO2-microRNA cluster controls oral cancer stemness ability and cancer progression

Abstract

Abstract Cancer recurrence and metastasis are the primary reasons for treatment failure in late-stage oral cancer. Cancer stem cells are the root of cancer recurrence and metastasis. By using the microRNAome analysis of Taiwan OSCC cohort, we found miR-876-3p was highly correlated to OSCC recurrence. The precursor miR-876 promoted in vitro OSCC cell proliferation, migration, and cancer stemness and regulated several cancer stemness-relative genes such as NANOG, OCT4, and LIN28A expression. miR-876 and miR-873 are located in the second intron of the 5’-untransalation region (5’-UTR) at the alternative variant leucine-rich repeat and Ig domain containing 2 (LINGO2). Interestingly, only OSCC cells presented LINGO2 protein expression but did not show in primary oral keratinocytes (HOK). The unique CpG islands at the alternative transcription start site of LINGO2 hinted at crucial epigenetic regulation that controls LINGO2 activation. Silencing of LINGO2 expression reduced OSCC cell growth and cancer stemness abilities. LINGO2 expression was higher in OSCC tumor tissue than in adjacent normal tissue in both Taiwan and The Cancer Genome Atlas (TCGA) head and neck cancer cohorts. Moreover, LINGO2 also served as a poor prognostic marker in cancer patients' overall and recurrent free survival time. In summary, we found a novel LINGO2-microRNA cluster that regulates OSCC stemness and metastasis abilities. Those cancer specific expressions may provide a new therapy niche in OSCC cancer therapy. Citation Format: Wei-Min Chang, Li-Jie Li, Che-Hsuan Lin, Michael Hsiao, Peter Mu-Hsin Chang. LINGO2-microRNA cluster controls oral cancer stemness ability and cancer progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB270.