Long noncoding RNA TCONS_00026334 is involved in suppressing the progression of colorectal cancer by regulating miR-548n/TP53INP1 signaling pathway

被引:7
|
作者
Zhu, Mingming [1 ]
Luo, Yang [2 ]
Xu, Antao [1 ]
Xu, Xitao [1 ]
Zhong, Ming [2 ]
Ran, Zhihua [1 ]
机构
[1] Shanghai Jiao Tong Univ, Shanghai Inst Digest Dis,Sch Med,Renji Hosp, Div Gastroenterol & Hepatol,Key Lab Gastroenterol, Minist Hlth,Shanghai Inflammatory Bowel Dis Res C, Shanghai, Peoples R China
[2] Shanghai Jiao Tong Univ, Sch Med, Ren Ji Hosp, Dept Gastrointestinal Surg, 160 Pujian Rd, Shanghai 200127, Peoples R China
来源
CANCER MEDICINE | 2020年 / 9卷 / 22期
基金
中国国家自然科学基金;
关键词
CELL; METASTASIS; EXPRESSION; TARGET; GENE;
D O I
10.1002/cam4.3473
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Recently, long noncoding RNAs (lncRNAs) were recognized as significant therapeutic targets in tumors. Our previous microarray analysis showed that lncRNATCONS_000026334expression was reduced in metastatic colorectal cancer (CRC) tissues. The objective of this study was to research the biological functions ofTCONS_000026334and the potential mechanism during the development of CRC.TCONS_00026334transcription levels were detected in CRC tissues from 86 patients and different CRC cell lines. The clinical prognosis factors related to TCONS_00026334 expression were then analyzed.TCONS_000026334was overexpressed from plasmid pcDNA3.1-TCONS_ 000026334 or knocked down using a small interfering RNA (siRNA). Furthermore, bioinformatics approach and luciferase reporter gene assays were utilized to search for candidate miRNAs of TCONS_00026334 and identify the downstream target genes. The results indicated thatTCONS_00026334expression in 86 CRC tissues was markedly lower than that in non-cancerous tissues. The aberrant expression ofTCONS_00026334correlated negatively with larger tumor size, distant metastasis, serological carcinoembryonic antigen level, and unfavorable survival of patients with CRC.TCONS_00026334overexpression could inhibit the aggressive phenotypes of CRC invitroand invivo. Conversely,TCONS_00026334silencing accelerated CRC cell proliferation and invasion. We then verified thatTCONS_00026334upregulated the expression level ofTP53INP1, a target gene of miR-548n, via direct binding to miR-548n as a competing endogenous RNA. Taken together, our study showed thatTCONS_00026334acts as an anti-tumor and anti-metastatic gene by regulating the miR548n/TP53INP1axis in the development of CRC.
引用
收藏
页码:8639 / 8649
页数:11
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