LncRNA NEAT1 remodels chromatin to promote the 5-Fu resistance by maintaining colorectal cancer stemness

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Abstract

Resistance of chemotherapy is one of causes of recurrence and poor prognosis in patients with colorectal cancer (CRC). The role of differentially expressed long non-coding RNA (lncRNA) in 5-fluorouracil (5-Fu) resistance has not been fully elucidated. Here we observed that lncRNA NEAT1 was associated with 5-Fu resistance in CRC. Our Functional studies showed that NEAT1 promoted 5-Fu resistance in colorectal cells. In addition, A-TAC sequencing and chromatin immunoprecipitation (ChIP) showed that NEAT1 affected chromatin remodeling, increased the acetylation levels of histones, increased their enrichment at the promoters of ALDH1 and c-Myc, and promoted the expression of ALDH1 and c-Myc. Taken together, our study suggested that NEAT1 promoted 5-Fu resistance and cancer stemness by remodeling chromatin. Our finding provides a novel role of NEAT1 and may provide a new strategy for the treatment of CRC 5-Fu resistance.

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Zhu, Y., Hu, H., Yuan, Z., Zhang, Q., Xiong, H., Hu, Z., … Tang, Q. (2020). LncRNA NEAT1 remodels chromatin to promote the 5-Fu resistance by maintaining colorectal cancer stemness. Cell Death and Disease, 11(11). https://doi.org/10.1038/s41419-020-03164-8

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