期刊
CANCER CELL INTERNATIONAL
卷 21, 期 1, 页码 -出版社
BMC
DOI: 10.1186/s12935-021-02209-y
关键词
LBX2-AS1; Colorectal cancer; M6A; 5-FU; ceRNA
类别
资金
- National Key Research and Development Program of China [2018YFC1004900, 2018YFC1005002]
- National Natural Science Foundation of China [81672350, 81872225, 81871988, 32000542]
LBX2-AS1 is significantly upregulated in colorectal cancer and positively correlated with aggressive disease characteristics, serving as an independent prognostic indicator. Mechanistically, LBX2-AS1 in CRC is regulated by METTL3-dependent m6A methylation and acts as a ceRNA to promote 5-fluorouracil resistance.
Background Recent reports suggest that the long non-coding RNA LBX2 antisense RNA 1 (LBX2-AS1) acts as an important regulator in cancer progression, but its significance in colorectal cancer (CRC) remains undetermined. Methods LBX2-AS1 expression levels in CRC were determined from the GEPIA database and CRC tissues to investigate clinical relevance. meRIP-PCR assays investigated the molecular mechanisms underlying the function of m6A in LBX2-AS1. Loss of function experiments was used to define the role of LBX2-AS1 in the progression of CRC. The ceRNA function of LBX2-AS1 was evaluated by RNA immunoprecipitation. In vitro and PDX models were used to determine if LBX2-AS1 promotes 5-fluorouracil resistance. Results Data from the TCGA and our institutional patient cohorts established that LBX2-AS1 levels were significantly upregulated in most CRC tissues relative to normal adjacent colon tissues. Moreover, LBX2-AS1 levels were positively correlated with aggressive disease characteristics, constituting an independent prognostic indicator of overall patient survival. Mechanistic investigations suggested that the increased LBX2-AS1 in CRC was mediated by METTL3-dependent m6A methylation. In vitro experiments indicated that knockdown of LBX2-AS1 inhibited CRC proliferation, migration and invasion with this phenotype linked to LBX2-AS1-mediated regulation of AKT1, acting as a ceRNA to sponge miR-422a. Ex vivo analysis of patient-derived CRC xenografts showed that low LBX2-AS1 expression cases exhibited 5-FU responsiveness and clinical investigations confirmed that low LBX2-AS1 expression was associated with improved clinical benefits from 5-FU therapy. Conclusions Together these results suggest that LBX2-AS1 may serve as a therapeutic target and predictor of 5-FU benefit in CRC patients.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据