Roles of DANCR/microRNA-518a-3p/MDMA ceRNA network in the growth and malignant behaviors of colon cancer cells

Abstract

Background The competing endogenous RNA (ceRNA) networks of long non-coding RNAs (lncRNAs) and microRNAs (miRs) have aroused wide concerns. The study aims to investigate the roles of lncRNA DANCR-associated ceRNA network in the growth and behaviors of colon cancer (CC) cells. Methods Differentially expressed lncRNAs between CC and paracancerous tissues were analyzed using microarrays and RT-qPCR. Follow-up studies were conducted to evaluate the correlation between DANCR expression and prognosis of CC patients. Loss-of-functions of DANCR were performed to identify its role in the malignant behaviors of CC cells. Sub-cellular localization of DANCR and the potential targets of DANCR were predicted and validated. Cells with inhibited DANCR were implanted into nude mice to evaluate the tumor formation and metastasis in vivo. Results DANCR was highly-expressed in CC tissues and cell lines, and higher levels of DANCR were linked with worse prognosis and less survival time of CC patients. Silencing of DANCR inhibited proliferation, viability, metastasis and resistance to death of CC cells. DANCR was found to be sub-localized in cytoplasmic matrix and to mediate murine double minute 2 (MDM2) expression through sponging miR-518a-3p in CC cells, during which the Smad2/3 signaling was activated. Likewise, silencing of DANCR in CC cells inhibited tumor formation and metastasis in vivo. Conclusion This study provided evidence that silencing of DANCR might inhibit the growth and metastasis of CC cells through the DANCR/miR-518a-3p/MDM2 ceRNA network and the defect of Smad2/3 while activation of the p53 signaling pathways. This study may offer novel insights in CC treatment.

RETRACTED ARTICLE: Long non-coding RNA HOXA11 antisense RNA upregulates spermatogenesis-associated serine-rich 2-like to enhance cisplatin resistance in laryngeal squamous cell carcinoma by suppressing microRNA-518a

“…The biological role and function of miR-518a have been identified in several cancers. For example, miR-518a overcame CDDP resistance in colon cancer by targeting MDMA [ 31 ]. Moreover, Li et al revealed that HOXA11-AS enhanced cell viability and invasion via miR-518a in oral squamous cell carcinoma [ 32 ].…”

miR-518a-3p Suppresses Triple-Negative Breast Cancer Invasion and Migration Through Regulation of TMEM2

“…MiR-518a-3p inhibits colorectal cancer cell growth through targeting NF-κB-inducing kinase, 10 and knockdown of miR-518a-3p promotes colon cancer cell migration and invasion via up-regulation of murine double minute 2. 11 Our results confirmed the anti-tumor effects of miR-518a-3p against migration and invasion of TNBC, revealing its potential clinical application in TNBC. Moreover, TMEM2 was validated as a target of miR-518a-3p in TNBC.…”

“…9 MiR-518a-3p was reported to be an anti-tumor effector for colorectal cancer 10 and participates in malignant behavior of colon cancer. 11 However, the role of miR-518a-3p in TNBC remains elusive. TMEM2 (transmembrane protein 2), a single-pass transmembrane domain protein, functions as hyaluronidase to degrade hyaluronic acid.…”

miRNA-518a-3p inhibits hepatocarcinogenesis by suppressing ZNF281

“…3.1 miR-518a-3p was downregulated in HCC tumor tissues and correlated with prognosis of HCC patients According to previous studies, a reduced expression of miR-518a-3p has been shown in CRC cells as well as CRC tissues [7,12] . Thus, in order to illustrate the correlation between miR-518a-3p expression and HCC, its expression level was detected by RT-qPCR analysis.…”