Lnc5q21.2, a novel long intergenic RNA, sensitizes colorectal cancer cells to ATR inhibitor by activating Wnt pathway

作者：Meiying Zhang, Cheng Zhu, Aiai Gao, James G. Herman, François Fuks, Jianjun Luo, Xiaomo Su, Hengmi Cui, Runsheng Chen, Mingzhou Guo · 发表于：Journal of Translational Internal Medicine · 年份：2025 · DOI：10.1515/jtim-2025-0040 · 被引用次数：2 · 研究领域：Cancer-related molecular mechanisms research、Circular RNAs in diseases、RNA Research and Splicing

Abstract Background and objectives Colorectal cancer (CRC) is still the leading cause of cancer-related death. With the recognizing the importance of long non-coding RNA (LncRNA) in development and cancer, it is urgently to identify new LncRNA and understand the mechanism to develop novel therapeutic strategies. Methods Nine CRC cell lines, 52,146 and 285 cases of normal colorectal mucosa, adenoma and CRC samples were utilized. Northern blot, rapid amplification of cloned cDNA ends, RNA pulldown, Mass spectrum, RNA immunoprecipitation, CRISPR/Cas9, fluorescence in situ hybridization assays and xenograft mice model were employed. Results Lnc5q21.2 is identified to be a novel long intergenic non-coding RNA and its full length is 668 nt. Lnc5q21.2 is mainly located in cell nucleus and its expression is regulated by N 6 -methyladenine (6mA) modification. Compared to adjacent tissue, the levels of Lnc5q21.2 were increased significantly in CRC samples ( P < 0.001), with a progression tendency from noncancerous colorectal mucosa, adjacent tissue, adenoma to CRC samples ( P < 0.001). Lnc5q21.2 highly expression is associated with alcohol consumption and poor prognosis (both P < 0.05). Lnc5q21.2 promotes cell proliferation, migration, invasion and cell cycle progression. Lnc5q21.2 activates Wnt signaling by interacting with homeobox A10 (HOXA10) and down regulating empty spiracles homeobox 2 expression. Further study demonstrates that Lnc5q21.2 promotes DNA damage repair by e...