Dataset Information

Circ_0031242 Silencing Mitigates the Progression and Drug Resistance in DDP-Resistant Hepatoma Cells by the miR-924/POU3F2 Axis.

ABSTRACT:

Background

Circular RNAs (circRNAs) have been implicated in the progression and chemoresistance development of hepatocellular carcinoma (HCC). However, the precise parts of circ_0031242 in HCC chemoresistance are still not fully understood.

Methods

The levels of circ_0031242, miR-924 and POU class 3 homeobox 2 (POU3F2) were detected by quantitative real-time polymerase chain reaction (qRT-PCR) assay or Western blot analysis. IC₅₀ value for cisplatin (DDP) and cell viability were measured by the cell counting kit-8 (CCK-8) assay. Cell migration, invasion and apoptosis were assessed by transwell assay and flow cytometry, respectively. Targeted correlations among circ_0031242, miR-924 and POU3F2 were verified by the dual-luciferase reporter and RNA immunoprecipitation (RIP) assays.

Results

Our data revealed that circ_0031242 was associated with HCC resistance to DDP. The silencing of circ_0031242 diminished DDP resistance, suppressed cell viability, migration, invasion and promoted apoptosis of DDP-resistant HCC cells (Huh7-R and SNU-387-R) in vitro, as well as enhanced DDP sensitivity in vivo. Mechanistically, circ_0031242 directly interacted with miR-924 by binding to miR-924. Moreover, miR-924 was a downstream effector of circ_0031242 function. POU3F2 was a direct target of miR-924, and miR-924 overexpression regulated DDP-resistant HCC cell progression and DDP resistance by down-regulating POU3F2. Furthermore, circ_0031242 modulated POU3F2 expression through sponging miR-924.

Conclusion

Our findings identified that circ_0031242 functioned as an important regulator in DDP-resistant HCC cell progression and DDP resistance through the miR-924/POU3F2 axis, illuminating circ_0031242 as a potential therapeutic target for the chemoresistant HCC.

SUBMITTER: Fan W

PROVIDER: S-EPMC7847388 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Circ_0031242 Silencing Mitigates the Progression and Drug Resistance in DDP-Resistant Hepatoma Cells by the miR-924/POU3F2 Axis.

Fan Wei W Chen Lei L Wu Xiaojuan X Zhang Tong T

Cancer management and research 20210126

<h4>Background</h4>Circular RNAs (circRNAs) have been implicated in the progression and chemoresistance development of hepatocellular carcinoma (HCC). However, the precise parts of circ_0031242 in HCC chemoresistance are still not fully understood.<h4>Methods</h4>The levels of circ_0031242, miR-924 and POU class 3 homeobox 2 (POU3F2) were detected by quantitative real-time polymerase chain reaction (qRT-PCR) assay or Western blot analysis. IC<sub>50</sub> value for cisplatin (DDP) and cell viabi ...[more]

PMID: 33531841

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Project description:Myocarditis is an inflammatory disease of the heart muscle most commonly caused by viral infection and often maintained by autoimmunity. Virus-induced tissue damage triggers chemokine production and, subsequently, immune cell infiltration with pro-inflammatory and pro-fibrotic cytokine production follows. In patients, the overall inflammatory burden determines the disease outcome. Following the aim to define specific molecules that drive both immunopathology and/or autoimmunity in inflammatory heart disease, here we report on increased expression of colony stimulating factor 1 (CSF-1) in patients with myocarditis. CSF-1 controls monocytes originating from hematopoietic stem cells and subsequent progenitor stages. Both, monocytes and macrophages are centrally involved in mediating tissue damage and fibrotic scarring in the heart. CSF-1 influences monocytes via engagement of CSF-1 receptor, and it is also produced by cells of the mononuclear phagocyte system themselves. Based on this, we sought to modulate the virus-triggered inflammatory response in an experimental model of Coxsackievirus B3-induced myocarditis by silencing the CSF-1 axis in myeloid cells using nanoparticle-encapsulated siRNA. siCSF-1 inverted virus-mediated immunopathology as reflected by lower troponin T levels, a reduction of accumulating myeloid cells in heart tissue and improved cardiac function. Importantly, pathogen control was maintained and the virus was efficiently cleared from heart tissue. Since viral heart disease triggers heart-directed autoimmunity, in a second approach we investigated the influence of CSF-1 upon manifestation of heart tissue inflammation during experimental autoimmune myocarditis (EAM). EAM was induced in Balb/c mice by immunization with a myocarditogenic myosin-heavy chain-derived peptide dissolved in complete Freund's adjuvant. siCSF-1 treatment initiated upon established disease inhibited monocyte infiltration into heart tissue and this suppressed cardiac injury as reflected by diminished cardiac fibrosis and improved cardiac function at later states. Mechanistically, we found that suppression of CSF-1 production arrested both differentiation and maturation of monocytes and their precursors in the bone marrow. In conclusion, during viral and autoimmune myocarditis silencing of the myeloid CSF-1 axis by nanoparticle-encapsulated siRNA is beneficial for preventing inflammatory tissue damage in the heart and preserving cardiac function without compromising innate immunity's critical defense mechanisms.

Dataset Information

Circ_0031242 Silencing Mitigates the Progression and Drug Resistance in DDP-Resistant Hepatoma Cells by the miR-924/POU3F2 Axis.

Background

Methods

Results

Conclusion

Publications

Circ_0031242 Silencing Mitigates the Progression and Drug Resistance in DDP-Resistant Hepatoma Cells by the miR-924/POU3F2 Axis.

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