e15587 Background: Long noncoding RNAs (lncRNA) have been implicated in cancer but most of them remain largely unstudied. Methods: In this study, we identified a NSUN2 methylated lncRNA (NMR), which is significantly upregulated in esophageal squamous cell carcinoma (ESCC), functions as a key regulator of ESCC tumor metastasis and drug resistance. Results: In microarray data of 119 paired ESCC and normal tissues, NMR was significantly overexpressed in ESCC (P < 0.001), and overexpression of NMR indicated poor overall survival of ESCC patients (P = 0.003); in RNA sequencing data of 20 cancer types from TCGA, including 426 head and neck squamous cell carcinoma (HNSC) patients, NMR was significantly upregulated in HNSC tissues (P < 0.01), and patients with higher T stage, N stage, and m stage had significantly higher NMR expression (P < 0.05). Dysregulation of NMR was also validated in an independent cohort with 83 ESCC patients. Consistently, NMR was significantly overexpressed in ESCC (P < 0.001), and high NMR expression was significantly associated with lymph node metastasis and poor overall survival (P < 0.05). Functional experiments demonstrated that NMR could promote tumor cell migration and invasion, inhibit cisplatin-induced apoptosis and increase drug resistance in ESCC cells. Mechanistically, transcription of NMR could be upregulated by NF-κB activation after IL-1β and TNF-α treatment. RNA sequencing after interference highlighted alterations in collagen metabolic process and ERK1 and ERK2 cascade. Further validation proved that NMR could promote the expression of MMP3 and MMP10, at least partially by ERK1/2 pathway. Conclusions: Taken together, these findings suggest that NMR functions as an oncogenic gene in ESCC and may serve as novel biomarker and therapeutic target in ESCC.
AB018. Clinical relevance of PD-L1 and PD-L2 in patients with esophageal squamous cell carcinoma
