TY - JOUR
T1 - Antisense lncRNA LDLRAD4-AS1 promotes metastasis by decreasing the expression of LDLRAD4 and predicts a poor prognosis in colorectal cancer
AU - Mo, Shaobo
AU - Zhang, Long
AU - Dai, Weixing
AU - Han, Lingyu
AU - Wang, Renjie
AU - Xiang, Wenqiang
AU - Wang, Zhimin
AU - Li, Qingguo
AU - Yu, Jun
AU - Yuan, Jihang
AU - Cai, Sanjun
AU - Cai, Guoxiang
N1 - Funding Information:
This study was supported by the Grant of National Natural Science Foundation of China (Nos. 81572351 and 81871958), the National Key R&D Program of China (Nos. 2016YFC0905300 and 2016YFC0905301), the Grant of Science and Technology Commission of Shanghai Municipality (No. 16401970502), Shanghai Shenkang Program (No. SHDC12014206), and the development fund for Shanghai talents (No. 2017120).
Publisher Copyright:
© 2020, The Author(s).
PY - 2020/2/1
Y1 - 2020/2/1
N2 - Long noncoding RNAs (lncRNAs) have been revealed to play critical roles in tumor initiation and progression. The antisense lncRNA LDLRAD4-AS1 is the longest lncRNA of LDLRAD4, and its expression levels, cellular localization, precise function, and mechanism in colorectal cancer (CRC) remain unknown. In this study, we observed that lncRNA LDLRAD4-AS1 was located in the nucleus of CRC cells and that lncRNA LDLRAD4-AS1 was upregulated in most CRC specimens and cell lines. Overexpression of lncRNA LDLRAD4-AS1 was correlated with poor prognosis in CRC patients. LncRNA LDLRAD4-AS1 upregulation enhanced the migration and invasion of CRC cells in vitro and facilitated CRC metastasis in vivo. Mechanistic investigations suggested that lncRNA LDLRAD4-AS1 could decrease the expression of LDLRAD4 by disrupting the stability of LDLRAD4 mRNA, resulting in epithelial-to-mesenchymal transition (EMT) through upregulating Snail, thereby promoting metastasis in CRC. Our results demonstrated a previously unrecognized LDLRAD4-AS1-LDLRAD4-Snail regulatory axis involved in epigenetic and posttranscriptional regulation that contributes to CRC progression and metastasis.
AB - Long noncoding RNAs (lncRNAs) have been revealed to play critical roles in tumor initiation and progression. The antisense lncRNA LDLRAD4-AS1 is the longest lncRNA of LDLRAD4, and its expression levels, cellular localization, precise function, and mechanism in colorectal cancer (CRC) remain unknown. In this study, we observed that lncRNA LDLRAD4-AS1 was located in the nucleus of CRC cells and that lncRNA LDLRAD4-AS1 was upregulated in most CRC specimens and cell lines. Overexpression of lncRNA LDLRAD4-AS1 was correlated with poor prognosis in CRC patients. LncRNA LDLRAD4-AS1 upregulation enhanced the migration and invasion of CRC cells in vitro and facilitated CRC metastasis in vivo. Mechanistic investigations suggested that lncRNA LDLRAD4-AS1 could decrease the expression of LDLRAD4 by disrupting the stability of LDLRAD4 mRNA, resulting in epithelial-to-mesenchymal transition (EMT) through upregulating Snail, thereby promoting metastasis in CRC. Our results demonstrated a previously unrecognized LDLRAD4-AS1-LDLRAD4-Snail regulatory axis involved in epigenetic and posttranscriptional regulation that contributes to CRC progression and metastasis.
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U2 - 10.1038/s41419-020-2338-y
DO - 10.1038/s41419-020-2338-y
M3 - Article
C2 - 32111819
AN - SCOPUS:85080840816
SN - 2041-4889
VL - 11
JO - Cell Death and Disease
JF - Cell Death and Disease
IS - 2
M1 - 155
ER -