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Circular RNA circCSPP1 knockdown attenuates doxorubicin resistance and suppresses tumor progression of colorectal cancer via miR-944/FZD7 axis.

TLDR
In this article, the functional mechanism of circCSPP1 in colorectal cancer (CRC) was revealed by quantitatively detecting the expression of circSPP 1, miR-944 and FZD7.
Abstract
Circular RNAs (circRNAs) have been reported to play vital roles in colorectal cancer (CRC). However, only a few circRNAs have been experimentally validated and functionally described. In this research, we aimed to reveal the functional mechanism of circCSPP1 in CRC. 36 DOX sensitive and 36 resistant CRC cases participated in this study. The expression of circCSPP1, miR-944 and FZD7 were detected by quantitative real time polymerase chain reaction (qRT-PCR) and the protein levels of FZD7, MRP1, P-gp and LRP were detected by western blot. Cell proliferation, migration, invasion, and apoptosis were assessed by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT) assay, transwell assay, or flow cytometry analysis, respectively. The interaction between miR-944 and circCSPP1 or frizzled-7 (FZD7) was predicted by Starbase 3.0 and verified by the dual luciferase reporter assay, RNA immunoprecipitation (RIP) assay and RNA pull down assay. Xenograft tumor assay was performed to examine the effect of circCSPP1 on tumor growth in vivo. The expression of circCSPP1 and FZD7 was upregulated while miR-944 expression was downregulated in doxorubicin (DOX)-resistant CRC tissues and cells. CircCSPP1 knockdown significantly downregulated enhanced doxorubicin sensitivity, suppressed proliferation, migration, invasion, and induced apoptosis in DOX-resistant CRC cells. Interestingly, we found that circCSPP1 directly downregulated miR-944 expression and miR-944 decreased FZD7 level through targeting to 3′ untranslated region (UTR) of FZD7. Furthermore, circCSPP1 mediated DOX-resistant CRC cell progression and doxorubicin sensitivity by regulating miR-944/FZD7 axis. Besides, circCSPP1 downregulation dramatically repressed CRC tumor growth in vivo. Our data indicated that circCSPP1 knockdown inhibited DOX-resistant CRC cell growth and enhanced doxorubicin sensitivity by miR-944/FZD7 axis, providing a potential target for CRC therapy.

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Circular RNA in disease: Basic properties and biomedical relevance

TL;DR: This review focuses on the recently described functional relevance of disease-associated circRNAs as well as the potential ofcircRNAs in diverse clinical applications, and calls for a revised view of circRNA biogenesis, nuclear export, and stability control.
Journal ArticleDOI

CircHAS2 promotes the proliferation, migration, and invasion of gastric cancer cells by regulating PPM1E mediated by hsa-miR-944.

TL;DR: In this article, a specific circRNA, circHAS2, was upregulated in GC tissues and cells and was positively correlated with tumor metastasis, which is a new class of endogenous noncoding RNAs, which can be used as biomarkers and therapeutic targets for many tumors.
Journal ArticleDOI

Non-Coding RNA and Frizzled Receptors in Cancer

TL;DR: The most commonly described ncRNA molecules are microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and circular RNAs.
Journal ArticleDOI

Hsa_circ_0000098 is a novel therapeutic target that promotes hepatocellular carcinoma development and resistance to doxorubicin

TL;DR: In this article , a series of in vitro and in vivo experiments were undertaken to investigate the biological importance and underlying mechanisms of circ_0000098 in hepatocellular cancer (HCC).
Journal ArticleDOI

The Role of Circular RNAs in the Drug Resistance of Cancers

TL;DR: The potential roles and mechanisms of circRNAs in cancer drug resistance including the efflux of drugs, apoptosis, intervention with the TME (tumor microenvironment), autophagy, and dysfunction of DNA damage repair are summarized.
References
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Journal ArticleDOI

Analysis of relative gene expression data using real-time quantitative pcr and the 2(-delta delta c(t)) method

TL;DR: The 2-Delta Delta C(T) method as mentioned in this paper was proposed to analyze the relative changes in gene expression from real-time quantitative PCR experiments, and it has been shown to be useful in the analysis of realtime, quantitative PCR data.
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MicroRNAs: Genomics, Biogenesis, Mechanism, and Function

TL;DR: Although they escaped notice until relatively recently, miRNAs comprise one of the more abundant classes of gene regulatory molecules in multicellular organisms and likely influence the output of many protein-coding genes.
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A ceRNA Hypothesis: The Rosetta Stone of a Hidden RNA Language?

TL;DR: It is proposed that this "competing endogenous RNA" (ceRNA) activity forms a large-scale regulatory network across the transcriptome, greatly expanding the functional genetic information in the human genome and playing important roles in pathological conditions, such as cancer.
Journal ArticleDOI

Multidrug resistance in cancer: role of ATP–dependent transporters

TL;DR: The ability to predict and circumvent drug resistance is likely to improve chemotherapy, and it has become apparent that resistance exists against every effective drug, even the authors' newest agents.
Journal ArticleDOI

Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project

Ewan Birney, +320 more
- 14 Jun 2007 - 
TL;DR: Functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project are reported, providing convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts.
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