Mechanistic Investigation of Linc00963 on Promoting Lymph Node Metastasis and Drug Resistance through Abcb5 Regulation and Its Potential Theranostic Value during Oral Carcinogenesis

Oral cancer is one of the common cancers for the past few years, and its prevalence remains high in the male population of Taiwan. The main etiological factors of oral cancer are areca nut chewing, smoking, and drinking, and the metastasis and recurrence rate of oral cancer are hard to neglect. Hence, it is urgent to find a potential biomarker to monitor and a more effective treatment to prevent cancer progression. Recent studies have revealed that long noncoding RNAs (lncRNAs) play critical roles in tumor initiation, progression, metastasis, and prognosis. And the cancer recurrence, metastasis, and drug resistance have been attributed to the existence of cancer stemness. Our preliminary study has demonstrated that the expression of the LINC00963 was up-regulated in oral cancer tissues. We have found that downregulation of LINC00963 could inhibit CSC hallmarks, such as migration and invasion, indicating its potential to inhibit tumorigenesis and progression. Moreover, suppression of LINC00963 reduced the expression of stemness marker ALDH1, drug resistance marker ABCB5, and the ability of self-renewal. Analysis of data from The Cancer Genome Atlas (TCGA) revealed that LINC00963 was positively correlated with stemness markers (Sox2 and CD44) and drug resistance markers (ABCG2 and ABCB5). Hence, we sought to understand the molecular mechanism underlying LINC00963-regulated cancer stemness and drug resistance. Besides, bioinformatics software has predicted that ABCB5 may be the interaction factor of LINC00963, leading to the enhanced cancer stemness and drug resistance. Consequently, we will elucidate whether ABCB5 is the interactome of LINC00963. Apart from detailed mechanisms, we will evaluate the therapeutic potential and clinical usage of LINC00963 based on the achieving results. The following are the specific aims of this project: (1) To functionally characterize LINC00963 on cancer stemness, drug resistance, and metastasis of OSCC cells.; (2) To investigate whether the LINC00963-regulated cancer stemness and drug resistance are mediated by ABCB5; (3) To evaluate the theranostics potential and therapeutic relevance of LINC00963 in oral cancer.