Apobec-1 Complementation Factor (A1CF) Inhibits Epithelial-Mesenchymal Transition and Migration of Normal Rat Kidney Proximal Tubular Epithelial Cells

Huang, Liyuan; Wang, Hong‐Lian; Zhou, Yuru; Ni, Dongsheng; Hu, Yanxia; Long, Yaoshui; Liu, Jianing; Peng, Rui; Zhou, Li; Liu, Zhicheng; Lyu, Zhong-Shi; Mao, Zhizhong; Hao, Jin; Li, Yiman; Zhou, Qin

doi:10.3390/ijms17020197

Cited by 8 publications

(6 citation statements)

References 34 publications

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“…Similar results were observed using an MTT assay (Figure S2I-L), which is an alternative method to EdU for measuring cell proliferation. FCM data indicated that overexpression of A1CF decreased apoptosis (Figures S1B,F and S2A,E), whereas A1CF knockdown increased apoptosis (Figure S2C,D,G,H) of OSRC-2 and 786-O cells, which is consistent with the reported results in other tumor cells [17,18] or kidney epithelial cells [13].…”

Section: A1cf Promotes the Proliferation Of Renal Cancer Cells And De...supporting

confidence: 90%

“…More recently, another Sox2-cre-driven global deletion of A1cf in mice did not result in embryonic lethality because they bypassed the implantation stage [10]. In addition to the liver and small intestine, A1CF is highly expressed in the kidney [1,10,11] and has been genetically [12] and molecularly [13] associated with kidney function. Further phenotypic analysis indicates that A1CF loss results in water homeostasis defects and increases protein and solute concentrations in the kidney [10].…”

Section: Introductionmentioning

confidence: 99%

“…A1CF functions in specific mRNA nucleocytoplasmic shuttling, which is dependent upon insulin [15] or interaction with APOBEC1 [16]. Our previous studies have indicated that A1CF regulates cell growth by targeting the 3 ′ -UTR of Dkk1 mRNA [14,17] and is involved in many cellular processes, such as epithelial-mesenchymal transition (EMT) [13], cell proliferation [18], migration, and apoptosis [17] in proximal tubular epithelial cells and breast cancer cells.…”

Section: Introductionmentioning

confidence: 99%

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A1CF Binding to the p65 Interaction Site on NKRF Decreased IFN-β Expression and p65 Phosphorylation (Ser536) in Renal Carcinoma Cells

Liu,

Yang,

Weng

et al. 2024

IJMS

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Apobec-1 complementation factor (A1CF) functions as an RNA-binding cofactor for APO-BEC1-mediated C-to-U conversion during RNA editing and as a hepatocyte-specific regulator in the alternative pre-mRNA splicing of metabolic enzymes. Its role in RNA editing has not been clearly established. Western blot, co-immunoprecipitation (Co-IP), immunofluorescence (IF), methyl thiazolyl tetrazolium (MTT), and 5-ethynyl-2′-deoxyuridine (EdU) assays were used to examine the role of A1CF beyond RNA editing in renal carcinoma cells. We demonstrated that A1CF interacts with NKRF, independent of RNA and DNA, without affecting its expression or nuclear translocation; however, it modulates p65(Ser536) phosphorylation and IFN-β levels. Truncation of A1CF or deletion on NKRF revealed that the RRM1 domain of A1CF and the p65 binding motif of NKRF are required for their interaction. Deletion of RRM1 on A1CF abrogates NKRF binding, and the decrease in IFN-β expression and p65(Ser536) phosphorylation was induced by A1CF. Moreover, full-length A1CF, but not an RRM1 deletion mutant, promoted cell proliferation in renal carcinoma cells. Perturbation of A1CF levels in renal carcinoma cells altered anchorage-independent growth and tumor progression in nude mice. Moreover, p65(Ser536) phosphorylation and IFN-β expression were lower, but ki67 was higher in A1CF-overexpressing tumor tissues of a xenograft mouse model. Notably, primary and metastatic samples from renal cancer patients exhibited high A1CF expression, low p65(Ser536) phosphorylation, and decreased IFN-β levels in renal carcinoma tissues compared with the corresponding paracancerous tissues. Our results indicate that A1CF-decreased p65(Ser536) phosphorylation and IFN-β levels may be caused by A1CF competitive binding to the p65-combined site on NKRF and demonstrate the direct binding of A1CF independent of RNA or DNA in signal pathway regulation and tumor promotion in renal carcinoma cells.

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Section: A1cf Promotes the Proliferation Of Renal Cancer Cells And De...supporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A1CF Binding to the p65 Interaction Site on NKRF Decreased IFN-β Expression and p65 Phosphorylation (Ser536) in Renal Carcinoma Cells

Liu,

Yang,

Weng

et al. 2024

IJMS

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“…This observation is in contrast to Apobec1 knockout mice, which display decreased HDL (Nakamuta et al 1996). A1CF has been reported by multiple groups to be highly expressed in the kidney (Lellek et al 2000;Dur et al 2004) and has been genetically (Pattaro et al 2016) and molecularly (Huang et al 2016) associated with kidney function. Given this, we evaluated whether our A1CF-null model displayed any kidney-related defects.…”

Section: A1cf Has Novel Physiological Rolesmentioning

confidence: 82%

APOBEC1 complementation factor (A1CF) is dispensable for C-to-U RNA editing in vivo

Snyder

McCarty

Mehalow

et al. 2017

RNA

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Editing of the human and murine ApoB mRNA by APOBEC1, the catalytic enzyme of the protein complex that catalyzes C-to-U RNA editing, creates an internal stop codon within the APOB coding sequence, generating two protein isoforms. It has been long held that APOBEC1-mediated editing activity is dependent on the RNA binding protein A1CF. The function of A1CF in adult tissues has not been reported because a previously reported null allele displays embryonic lethality. This work aimed to address the function of A1CF in adult mouse tissues using a conditional A1cf allele. Unexpectedly, A1cf-null mice were viable and fertile with modest defects in hematopoietic, immune, and metabolic parameters. C-to-U RNA editing was quantified for multiple targets, including ApoB, in the small intestine and liver. In all cases, no changes in RNA editing efficiency were observed. Blood plasma analysis demonstrated a male-specific increase in solute concentration and increased cellularity in the glomeruli of male A1cf-null mice. Urine analysis showed a reduction in solute concentration, suggesting abnormal water homeostasis and possible kidney abnormalities exclusive to the male. Computational identification of kidney C-to-U editing sites from polyadenylated RNA-sequencing identified a number of editing sites exclusive to the kidney. However, molecular analysis of kidney C-to-U editing showed no changes in editing efficiency with A1CF loss. Taken together, these observations demonstrate that A1CF does not act as the APOBEC1 complementation factor in vivo under normal physiological conditions and suggests new roles for A1CF, specifically within the male adult kidney.

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“…Apobec-1 complementation factor (A1CF) belongs to heterogeneous nuclear ribonucleoproteins (hnRNP) family and is highly conserved across species. 5,6 It contains three non-identical RNA recognition motifs (RRM) and a unique C-terminal auxiliary domain. 7 A1CF participates in the post-transcriptional cytidine (C) to uridine (U) RNA editing of apolipoprotein-B (ApoB) messenger RNA (mRNA) by co-acting with APOBEC1.…”

Section: Introductionmentioning

confidence: 99%

Apobec-1 complementation factor regulates cell migration and apoptosis through Dickkopf1 by acting on its 3′ untranslated region in MCF7 cells

Yan

et al. 2017

Tumour Biol.

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A1CF (apobec-1 complementation factor) acts as a component of the apolipoprotein-B messenger RNA editing complex. Previous researches mainly focused on its post-transcriptional cytidine to uridine RNA editing. However, few study reported its role in progression of breast carcinoma cells. Wound healing assay and flow cytometry were applied to detect the migration and apoptosis; western blot, real-time polymerase chain reaction, and dual-luciferase assays were applied to investigate the potential regulation mechanism of A1CF-mediated cell migration and apoptosis. Knockdown of A1CF decreased cell migration and enhanced cell apoptosis in MCF7 cells in vitro. Western blot analysis showed that knockdown of A1CF decreased Dickkopf1 but increased c-Myc and β-catenin expression, and overexpression of A1CF can get opposite results. Knockdown of Dickkopf1 in A1CF-overexpressed cells decreased cell migration and enhanced cell apoptosis compared with A1CF-overexpressed cells. Luciferase-fused 3′ untranslated region of human Dickkopf1 activity was highly upregulated in A1CF-overexpressed MCF7 cells, but this upregulation can be inhibited by mutating conserved binding motifs of Dickkopf1 3′ untranslated region. A1CF played a crucial role in cell migration and survival through affecting 3′ untranslated region of Dickkopf1 to upregulate its expression in MCF7 cells.

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Apobec-1 Complementation Factor (A1CF) Inhibits Epithelial-Mesenchymal Transition and Migration of Normal Rat Kidney Proximal Tubular Epithelial Cells

Cited by 8 publications

References 34 publications

A1CF Binding to the p65 Interaction Site on NKRF Decreased IFN-β Expression and p65 Phosphorylation (Ser536) in Renal Carcinoma Cells

A1CF Binding to the p65 Interaction Site on NKRF Decreased IFN-β Expression and p65 Phosphorylation (Ser536) in Renal Carcinoma Cells

APOBEC1 complementation factor (A1CF) is dispensable for C-to-U RNA editing in vivo

Apobec-1 complementation factor regulates cell migration and apoptosis through Dickkopf1 by acting on its 3′ untranslated region in MCF7 cells

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