Antiviral RNA Silencing Initiated in the Absence of RDE-4, a Double-Stranded RNA Binding Protein, in Caenorhabditis elegans

Guo, Xingchen; Zhang, Rui; Wang, Jeffrey; Lu, Rongwen

doi:10.1128/jvi.01305-13

Cited by 17 publications

(24 citation statements)

References 52 publications

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“…SKOV3 and OVCAR3 cells transduced with lentiviral ASAP1 or control vector were plated into 6-well plates (200 cells/well) in triplicate and then stained with 0.1% Crystal Violet following culture for two weeks. Cell colonies were counted as described previously (14).…”

Section: Lentiviral Vector Productionmentioning

confidence: 99%

Lentiviral vector mediated-ASAP1 expression promotes epithelial to mesenchymal transition in ovarian cancer cells

et al. 2018

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Abstract. Ovarian cancer is one of the most common malignancies in women and has a high mortality rate due to metastatic progression and tumor recurrence. ASAP1 (ArfGAP with SH3 Domain, Ankyrin Repeat and PH Domain 1) is an ADP-ribosylation factor GTPase-activating protein, which is involved in tumor metastasis. However, the role of ASAP1 in ovarian cancer is completely unknown. The present study reported that ASAP1 was highly expressed in ovarian carcinoma, and expression positively-correlated with overall poor survival and prognosis of patients. Lentiviral vector mediated ASAP1 expression promoted cell migration and invasion in ovarian cancer cell lines SKOV3 and OVCAR3. In addition, ASAP1 promoted cell proliferation, survival and inhibited chemotherapy drug paclitaxel-induced cell apoptosis. Furthermore, ASAP1 expression promoted epithelial to mesenchymal transition (EMT) by upregulating the mesenchymal cell markers N-cadherin and vimentin, and downregulating epithelial cell marker E-cadherin in the ovarian cancer cell lines. The data indicate for the first time that ASAP1 exhibits an oncogenic role by promoting EMT in ovarian cancer cells. IntroductionOvarian cancer is one of the most common gynecological malignancies with a high mortality rate (1). In 2017, 22,440 new cases and 14,080 deaths of ovarian cancer were estimated to occur in the United States (2). At the time of diagnosis, the majority of ovarian cancer patients have already progressed to advanced disease, due to the lack of early clinical symptoms, which results in high mortality (3). However, the molecular mechanisms underlying the tumor metastasis and chemoresistance in ovarian cancer are not well understood. The epithelial-mesenchymal transition (EMT) contributes to the tumor metastasis and chemoresistance (4). EMT is a biological process accompanied by the loss of cell adherence junctions and apical-basal polarity, and acquisition of the mesenchymal phenotype to increase cell motility and invasiveness (5). EMT marker gene expression is altered during the EMT process with downregulation of epithelial markers such as E-cadherin and upregulation of mesenchymal markers, including Snai1 and 2, N-cadherin, vimentin, Zeb 1/2, and Twist1/2 (6,7). ASAP1 (ArfGAP with SH3 Domain, Ankyrin Repeat and PH Domain 1) protein has N-terminal BAR, PH, ARF GAP, ankyrin repeat, proline-rich, and C-terminal SH3 domains (8). ASAP1 expression is upregulated in a variety of cancers as compared to normal tissue, and correlates with poor survival and prognosis in colorectal, and neck and head cancer patients (9,10). In breast cancer ASAP1expression contributes to tumor invasion and metastasis (11). ASAP1 is upregulated in ovarian cancer and associated with poor patient survival and prognosis (12). However, the function of ASAP1 in ovarian cancer has not been investigated.In the present study, we investigated the role of ASAP1 in ovarian cancer cells using lentiviral vector mediated overexpression. We demonstrated that ASAP1 was highly expressed in ovarian cancer and as...

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Section: Lentiviral Vector Productionmentioning

confidence: 99%

Lentiviral vector mediated-ASAP1 expression promotes epithelial to mesenchymal transition in ovarian cancer cells

et al. 2018

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“…These observations suggest that DRH-1 might function as a sensor of viral RNA, analogous to RIG-I, but instead trigger an RNAi response (26). Others have argued that [17,28,43]). Virus infection and replication leads to the production of viral dsRNA that triggers the antiviral RNAi pathway.…”

Section: Nonnatural Virus Models (I) Flock House Virusmentioning

confidence: 99%

“…Interestingly, DCR-1 can also initiate primary vsiRNA production in the absence of RDE-4, albeit less efficiently (28). Therefore, the role of DRH-1 in antiviral RNAi remains enigmatic.…”

Section: Nonnatural Virus Models (I) Flock House Virusmentioning

confidence: 99%

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Caenorhabditis elegans as an Emerging Model for Virus-Host Interactions

Gammon

2017

J Virol

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Since 1999, Caenorhabditis elegans has been extensively used to study microbe-host interactions due to its simple culture, genetic tractability, and susceptibility to numerous bacterial and fungal pathogens. In contrast, virus studies have been hampered by a lack of convenient virus infection models in nematodes. The recent discovery of a natural viral pathogen of C. elegans and development of diverse artificial infection models are providing new opportunities to explore virushost interplay in this powerful model organism.KEYWORDS Caenorhabditis elegans, Flock House virus, innate immunity, Orsay virus, RNA interference, virus-host interactions, vesicular stomatitis virus I n the past 40 years, the free-living nematode Caenorhabditis elegans has been used in diverse fields such as neurobiology, RNA interference (RNAi), and pathogen-host interactions. As a model, C. elegans offers many advantages, including genetic tractability, small size, and inexpensive culture. Its sexually dimorphic nature and short reproductive cycle make genetic crosses and rearing large numbers of animals simple. As C. elegans naturally feeds on bacteria (1), one can often initiate intestinal infection by using the microbe of interest as a food source. Furthermore, the transparent body of C. elegans permits visualization of fluorescently tagged pathogens and tissue pathologies. Well-defined techniques for genetically modifying the laboratory strain (N2) make identifying nematode factors influencing pathogen susceptibilities relatively straightforward (2, 3). RNAi is also easily performed by feeding nematodes bacteria expressing double-stranded RNAs (dsRNAs) targeting the gene of interest. This "feeding" RNAi response spreads to most tissues and can be inherited, allowing inhibition of gene expression in adults and progeny.Although lacking the classic adaptive immunity found in vertebrates that relies on specialized immune cells, C. elegans employs a variety of innate and nonclassic adaptive immune responses that are shared with other metazoans (i.e., antiviral RNAi) (4, 5). An estimated 38% of the ϳ20,250 protein-encoding genes in C. elegans have human orthologs (6), and several antimicrobial pathways found in mammals are also found in worms (4,5,(7)(8)(9). Therefore, C. elegans can be used to explore conserved immunological mechanisms.Since the establishment of a Pseudomonas aeruginosa infection model in 1999 (10, 11), dozens of bacterial and fungal pathogens (including several that infect humans) have been shown to cause disease in C. elegans (reviewed in [1,9]). Studies of these predominantly extracellular pathogens have largely shaped our understanding of C. elegans immunity. However, with the recent discovery of natural intracellular pathogens of C. elegans (12, 13) and the development of nonnatural virus infection models (14-18), this is beginning to change.Here virus-C. elegans interaction models (Table 1) are discussed in terms of their features, advantages/disadvantages, and contributions to our understanding of C. elegan...

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“…In invertebrates, the systemic antiviral response utilises different mechanisms [43]. In C. elegans , the RNAi response is divided into primary and secondary steps and two types of siRNAs are produced.…”

Section: From Cell Intrinsic To Systemic Antiviral Immunitymentioning

confidence: 99%

Sensing viral RNAs by Dicer/RIG-I like ATPases across species

Paro

Imler

Meignin

2015

Current Opinion in Immunology

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Induction of antiviral immunity in vertebrates and invertebrates relies on members of the RIG-I-like receptor and Dicer families, respectively. Although these proteins have different size and domain composition, members of both families share a conserved DECH-box helicase domain. This helicase, also known as a duplex RNA activated ATPase, or DRA domain, plays an important role in viral RNA sensing. Crystallographic and electron microscopy studies of the RIG-I and Dicer DRA domains indicate a common structure and that similar conformational changes are induced by dsRNA binding. Genetic and biochemical studies on the function and regulation of DRAs reveal similarities, but also some differences, between viral RNA sensing mechanisms in nematodes, flies and mammals.

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Antiviral RNA Silencing Initiated in the Absence of RDE-4, a Double-Stranded RNA Binding Protein, in Caenorhabditis elegans

Cited by 17 publications

References 52 publications

Lentiviral vector mediated-ASAP1 expression promotes epithelial to mesenchymal transition in ovarian cancer cells

Lentiviral vector mediated-ASAP1 expression promotes epithelial to mesenchymal transition in ovarian cancer cells

Caenorhabditis elegans as an Emerging Model for Virus-Host Interactions

Sensing viral RNAs by Dicer/RIG-I like ATPases across species

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