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Open accessJournal ArticleDOI: 10.1186/S12935-021-01855-6

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

04 Mar 2021-Cancer Cell International (BioMed Central)-Vol. 21, Iss: 1, pp 153-153
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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Topics: Tumor progression (54%), Gene knockdown (52%), Cell growth (51%) ... show more
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5 results found


Open accessJournal ArticleDOI: 10.3389/FMOLB.2021.712546
04 Oct 2021-
Abstract: Frizzled receptors have been long recognized for their role in Wnt/β-catenin signaling, a pathway known for its tumorigenic effects. More recent studies of frizzled receptors include efforts to understand non-coding RNA (ncRNA) regulation of these receptors in cancer. It has become increasingly clear that ncRNA molecules are important for regulating the expression of both oncogenic and tumor-suppressive proteins. The three most commonly described ncRNA molecules are microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs). Here, we review ncRNA molecules that directly or indirectly affect frizzled protein expression and downstream signaling. Exploring these interactions highlights the potential of incorporating ncRNA molecules into cancer prevention and therapy strategies that target frizzled receptors. Previous investigations of frizzled receptors and ncRNA have established strong promise for a role in cancer progression, but additional studies are needed to provide the substantial pre-clinical evidence required to translate findings to clinical applications.

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Topics: Frizzled (65%), Wnt signaling pathway (53%), Non-coding RNA (52%)

1 Citations


Open accessJournal ArticleDOI: 10.1038/S41419-021-04158-W
Shuo Ma1, Xinliang Gu1, Lei Shen1, Yinhao Chen1  +3 moreInstitutions (1)
Abstract: Gastric cancer (GC) is considered one of the most common gastrointestinal malignancies worldwide. Circular RNAs (circRNAs) are a new class of endogenous noncoding RNAs, which can be used as biomarkers and therapeutic targets for many tumors. However, the role and potential regulatory mechanisms of circRNAs in GC remain unclear. In this study, we demonstrated that a specific circRNA, circHAS2, was upregulated in GC tissues and cells and was positively correlated with tumor metastasis. In vitro experiments demonstrated that circHAS2 knockdown or the addition of hsa-miR-944 mimics inhibited the proliferation, migration, and invasion ability of GC cells and affected the epithelial-mesenchymal transition. In addition, hsa-miR-944 interacted with protein phosphatase, Mg2+/Mn2+-dependent 1E (PPM1E), and was found to be a target gene of circHAS2. The upregulation of PPM1E reversed the effects of circHAS2 knockout on GC cells. The circHAS2/hsa-miR-944/PPM1E axis may be involved in the progression of GC; thus, circHAS2 may be a potential biomarker and therapeutic target for GC.

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Open accessJournal ArticleDOI: 10.3390/CANCERS13143395
06 Jul 2021-Cancers
Abstract: Colorectal cancer (CRC) is ranked as the second most commonly diagnosed disease in females and the third in males worldwide. Therefore, the finding of new more reliable biomarkers for early diagnosis, for prediction of metastasis, and resistance to conventional therapies is an important challenge in overcoming the disease. The current review presents circular RNAs (circRNAs) with their unique features as potential prognostic and diagnostic biomarkers in CRC. The review highlights the mechanism of action and the role of circRNAs with oncogenic functions in the CRC as well as the association between their expression and clinicopathological characteristics of CRC patients. The comprehension of the role of oncogenic circRNAs in CRC pathogenesis is growing rapidly and the next step is using them as suitable new drug targets in the personalized treatment of CRC patients.

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Open accessJournal ArticleDOI: 10.3892/OL.2021.12863
Mingying Zhang1, Shubin Wang1Institutions (1)
10 Jun 2021-Oncology Letters
Abstract: Colorectal cancer (CRC) is one of the most common types of malignant cancer worldwide and poses a significant burden on both the individual and healthcare systems. Despite advances in treatment options, advanced-stage CRC has a high mortality rate due to its heterogeneity, metastatic potential and/or delay in diagnosis. In recent years, an increasing number of studies have indicated that circular RNAs (circRNAs) serve important roles in several types of cancer, including CRC. Recent studies have revealed that circRNAs are aberrantly expressed in CRC tissues and function as oncogenic or tumor suppressive regulators of CRC carcinogenesis and development. Numerous circRNAs have been associated with the clinicopathological features of patients with CRC and have been considered as potential biomarkers for the diagnosis and prognosis of CRC, as well as targets for treatment. However, a deeper understanding of their potential function is required. In the present review, the current body of knowledge on the biogenesis and functions of CRC-associated circRNAs, and their potential value in clinical applications, such as in CRC diagnosis, prognosis and treatment, is discussed and summarized.

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39 results found


Journal ArticleDOI: 10.1006/METH.2001.1262
01 Dec 2001-Methods
Abstract: The two most commonly used methods to analyze data from real-time, quantitative PCR experiments are absolute quantification and relative quantification. Absolute quantification determines the input copy number, usually by relating the PCR signal to a standard curve. Relative quantification relates the PCR signal of the target transcript in a treatment group to that of another sample such as an untreated control. The 2(-Delta Delta C(T)) method is a convenient way to analyze the relative changes in gene expression from real-time quantitative PCR experiments. The purpose of this report is to present the derivation, assumptions, and applications of the 2(-Delta Delta C(T)) method. In addition, we present the derivation and applications of two variations of the 2(-Delta Delta C(T)) method that may be useful in the analysis of real-time, quantitative PCR data.

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Topics: MicroRNA 34a (52%), Cell wall organization (50%)

116,500 Citations


Open accessJournal ArticleDOI: 10.1016/S0092-8674(04)00045-5
David P. Bartel1Institutions (1)
23 Jan 2004-Cell
Abstract: MicroRNAs (miRNAs) are endogenous ∼22 nt RNAs that can play important regulatory roles in animals and plants by targeting mRNAs for cleavage or translational repression. 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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Topics: MicroRNA 34a (63%), Lin-4 microRNA precursor (56%), MicroRNA sequencing (55%) ... show more

30,422 Citations


Open accessJournal ArticleDOI: 10.1038/NATURE05874
14 Jun 2007-Nature
Abstract: We report the generation and analysis of 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. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examination of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded new mechanistic and evolutionary insights concerning the functional landscape of the human genome. Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function.

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Topics: ENCODE (67%), Genomics (57%), Genome (57%) ... show more

4,870 Citations


Open accessJournal ArticleDOI: 10.1038/NRC706
Abstract: Chemotherapeutics are the most effective treatment for metastatic tumours. However, the ability of cancer cells to become simultaneously resistant to different drugs--a trait known as multidrug resistance--remains a significant impediment to successful chemotherapy. Three decades of multidrug-resistance research have identified a myriad of ways in which cancer cells can elude chemotherapy, and it has become apparent that resistance exists against every effective drug, even our newest agents. Therefore, the ability to predict and circumvent drug resistance is likely to improve chemotherapy.

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4,754 Citations


Open accessJournal ArticleDOI: 10.1016/J.CELL.2011.07.014
Leonardo Salmena1, Laura Poliseno1, Yvonne Tay1, Lev Kats1  +1 moreInstitutions (1)
05 Aug 2011-Cell
Abstract: Here, we present a unifying hypothesis about how messenger RNAs, transcribed pseudogenes, and long noncoding RNAs "talk" to each other using microRNA response elements (MREs) as letters of a new language. We propose 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.

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Topics: Competing endogenous RNA (57%), Non-coding RNA (55%), Pseudogene (51%) ... show more

3,999 Citations