The carcinogenic complex lncRNA DUXAP8/EZH2/LSD1 accelerates the proliferation, migration and invasion of colorectal cancer.

PURPOSE:To elucidate the potential role of long non-coding RNA (lncRNA) DUXAP8 in the malignant progression of colorectal cancer (CRC) and its possible molecular mechanism. METHODS:The expression level of lncRNA DUXAP8 in CRC tissues and matched paracancerous tissues was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Meanwhile, its level in CRC patients with different tumor sizes and tumor grades was determined. The regulatory effects of DUXAP8 on the behaviors of CRC cells were evaluated by cell counting kit-8 (CCK-8), 5-Ethynyl-2'- deoxyuridine (EdU) and Transwell assay. The interaction between LSD1, EZH2 and DUXAP8 was evaluated by RNA-protein interactions and RIP assay. Linear regression analyses were conducted to examine the correlation between DUXAP8 and LSD1, EZH2. RESULTS:LncRNA DUXAP8 was upregulated in CRC tissues and cell lines. Its level remained higher in CRC with larger tumor size or higher tumor grade. Knockdown of DUXAP8 suppressed the proliferative, migratory and invasive abilities of DLD-1 and SW480 cells. Both RF classifier and SVM classifier predicted the pronounced accuracies of LSD1 and EZH2. RIP assay further demonstrated the interaction between DUXAP8 and LSD1, EZH2. Knockdown of LSD1 or EZH2 could attenuate the proliferative rate of CRC cells. Moreover, the mRNA levels of LSD1 and EZH2 were positively correlated with DUXAP8 in CRC. CONCLUSIONS:LncRNA DUXAP8 accelerates the malignant progression of CRC via positively regulating EZH2 and LSD1.

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