Long noncoding RNA LINC01578 drives colon cancer metastasis through a positive feedback loop with the NF‐κB/YY1 axis

Abstract

Metastasis accounts for poor prognosis of cancers and related deaths. Accumulating evidence has shown that long noncoding RNAs (lncRNAs) play critical roles in several types of cancer. However, which lncRNAs contribute to metastasis of colon cancer is still largely unknown. In this study, we found that lncRNA LINC01578 was correlated with metastasis and poor prognosis of colon cancer. LINC01578 was upregulated in colon cancer, associated with metastasis, advanced clinical stages, poor overall survival, disease-specific survival, and disease-free survival. Gain-of-function and loss-of-function assays revealed that LINC01578 enhanced colon cancer cell viability and mobility in vitro and colon cancer liver metastasis in vivo. Mechanistically, nuclear factor kappa B (NF-jB) and Yin Yang 1 (YY1) directly bound to the LINC01578 promoter, enhanced its activity, and activated LINC01578 expression. LINC01578 was shown to be a chromatin-bound lncRNA, which directly bound NFKBIB promoter. Furthermore, LINC01578 interacted with and recruited EZH2 to NFKBIB promoter and further repressed NFKBIB expression, thereby activating NF-jB signaling. Through activation of NF-jB, LINC01578 further upregulated YY1 expression. Through activation of the NF-jB/YY1 axis, LINC01578 in turn enhanced its own promoter activity, suggesting that LINC01578 and NF-jB/YY1 formed a positive feedback loop. Blocking NF-jB signaling abolished the oncogenic roles of LINC01578 in colon cancer. Furthermore, the expression levels of LINC01578, NFKBIB, and YY1 were correlated in clinical tissues. Collectively, this study demonstrated that LINC01578 promoted colon cancer metastasis via forming a positive feedback loop with NF-jB/YY1 and suggested that LINC01578 represents a potential prognostic biomarker and therapeutic target for colon cancer metastasis.

RETRACTED: LncRNA SNHG19 Promotes the Development of Non-Small Cell Lung Cancer via Mediating miR-137/E2F7 Axis

“…LncRNA refers to a large class of long-stranded RNA molecules that do not encode proteins and have transcripts of more than 200 bp, which were first discovered by researchers in 2002 during the largescale sequencing of mouse genome-wide cDNA libraries (6). Some studies have found that many lncRNAs are abnormally expressed in hepatocellular carcinoma, colorectal cancer, chronic lymphoblastic leukemia, and other malignant tumors (7,8). In recent years, lncRNA has received more and more attention in regulating the occurrence and development of lung cancer (9).…”

Upregulated long non‑coding RNA LincIN promotes tumor progression via the regulation of nuclear factor 90/microRNA‑7/HOXB13 in esophageal squamous cell carcinoma

“…Functional rescue assays demonstrated that the overexpression of miR-7 or depletion of HOXB13 attenuated the promoting effects of LincIN on ESCC cell growth, migration and invasion, which further suggested that miR-7/HOXB13 are critical mediators of the oncogenic roles of LincIN in ESCC. Similar roles of lncRNAs in miRNAs biogenesis have also been reported in other types of cancer, such as the promotion of miR-145 biogenesis by lncRNA-ATB in bladder cancer and the disruption of miR-125b biogenesis by LINC01578 in breast cancer ( 63 , 65 ). The detailed mechanisms underlying the inverse effects of lncRNAs on the biogenesis of different miRNAs warrant further investigation.…”

Long noncoding RNAs: functions and mechanisms in colon cancer

“…LncRNA LOC441461 knockdown suppresses growth and induces apoptosis and represses motility via the inhibition of PhoA/ROCK pathways in colon cancer [61]. Linc01578 enhances tumor metastasis via modulation of NF-κB and Yin Yang 1 (YY1) axis in colon cancer [57].…”