<scp>APOBEC</scp>3G is increasingly expressed on the human uterine cervical intraepithelial neoplasia along with disease progression

Iizuka, Takashi; Wakae, Kousho; Nakamura, Mitsuhiro; Kitamura, Koichi; Ono, Masanori; Fujiwara, Hiroshi; Muramatsu, Masamichi

doi:10.1111/aji.12703

Cited by 15 publications

(18 citation statements)

References 27 publications

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“…Next, the healthy growing follicles and corpora lutea were independently evaluated under a microscope by 3 gynecologic endocrinologists (14) without any information about the origin of each slide (Figure 2B and C), and then their numbers were finally determined (Figure 2A, asterisks). If the judgment of health conditions differed, the less favorable evaluation was selected, as reported previously (15, 16).…”

Section: Methodsmentioning

confidence: 99%

Time Restriction of Food Intake During the Circadian Cycle Is a Possible Regulator of Reproductive Function in Postadolescent Female Rats

Fujiwara

Nakata

Ono

et al. 2019

Current Developments in Nutrition

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Background We previously reported that skipping breakfast is associated with menstrual disorders of female college students during postadolescent maturation. Objective In this study, we investigated the effects of meal timing during circadian cycle on the ovarian function using young female rats. Methods Considering that rats are nocturnally active, 8-wk-old female Wistar rats were classified into 3 groups: fed during the daytime only (nonactive phase), night-time only (active phase), or control group I (without time or calorie restriction, free access to a standard caloric diet, 20.0% protein, 62.9% carbohydrate, and 7.0% fat, 3.95 kcal/g) for 4 wk. The changes in body weight and frequency of ovulation in each group were evaluated by a weight scale and a vaginal smear, respectively. At the end of the period of dietary restriction, ovaries were removed, and the numbers of growing follicles (mean diameter >250 µm) and corpora lutea (>600 µm) were examined using hematoxylin-eosin-stained tissue sections. In addition, 8-wk-old female rats were fed only during the night-time for 4 wk under a 20%-reduced food supply of the control group II (without any restriction). Results In the daytime-fed group, the frequency and number of ovulations were significantly decreased compared with those in the control group I ( P < 0.05), with a reduced body weight gain concomitant with about 20% of reduction in the daily food intake. In contrast, in the night-time-fed group, even when a 20% reduction in the daily food intake was loaded, their estrus cyclicity did not change despite significant reductions in weight gain and food intake compared with control group II. Conclusion These findings indicate that restricting food intake to the inactive phase impairs ovarian function in postadolescent female rats, suggesting that the timing of food intake during circadian cycle is one of the crucial factors interfering with the reproductive function.

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Section: Methodsmentioning

confidence: 99%

Time Restriction of Food Intake During the Circadian Cycle Is a Possible Regulator of Reproductive Function in Postadolescent Female Rats

Fujiwara

Nakata

Ono

et al. 2019

Current Developments in Nutrition

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“…Indeed, almost all cervical cancers and a significant fraction of head and neck cancers (HNSCC), all harboring frequent A3-related mutations, are associated with viral infections ( Vartanian et al, 2008 ; Lawrence et al, 2013 ). Additionally, A3G expression in HPV-induced uterine cervical intraepithelial neoplasia (CIN) and infiltration of A3G expressing CD3 positive T cells in CIN lesions were reported ( Iizuka et al, 2017 ). In contrast, the frequent occurrence of a characteristic mutational A3 signature ( Lawrence et al, 2013 ) in urothelial carcinoma (UC) is puzzling, as these tumors are thought to be caused predominantly by chemical carcinogens rather than viral infections ( Tolstov et al, 2014 ).…”

Section: Introductionmentioning

confidence: 99%

APOBEC3B Activity Is Prevalent in Urothelial Carcinoma Cells and Only Slightly Affected by LINE-1 Expression

et al. 2018

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The most common mutational signature in urothelial carcinoma (UC), the most common type of urinary bladder cancer is assumed to be caused by the misdirected activity of APOBEC3 (A3) cytidine deaminases, especially A3A or A3B, which are known to normally restrict the propagation of exogenous viruses and endogenous retroelements such as LINE-1 (L1). The involvement of A3 proteins in urothelial carcinogenesis is unexpected because, to date, UC is thought to be caused by chemical carcinogens rather than viral activity. Therefore, we explored the relationship between A3 expression and L1 activity, which is generally upregulated in UC. We found that UC cell lines highly express A3B and in some cases A3G, but not A3A, and exhibit corresponding cytidine deamination activity in vitro. While we observed evidence suggesting that L1 expression has a weak positive effect on A3B and A3G expression and A3B promoter activity, neither efficient siRNA-mediated knockdown nor overexpression of functional L1 elements affected catalytic activity of A3 proteins consistently. However, L1 knockdown diminished proliferation of a UC cell line exhibiting robust endogenous L1 expression, but had little impact on a cell line with low L1 expression levels. Our results indicate that UC cells express A3B at levels exceeding A3A levels by far, making A3B the prime candidate for causing genomic mutations. Our data provide evidence that L1 activation constitutes only a minor and negligible factor involved in induction or upregulation of endogenous A3 expression in UC.

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“…Furthermore, IFN-γ is assumed to be intimately associated with the elimination stage of the immunoediting paradigm [29]. It was reported that IFNs can induce A3G expression on the uterine cervical squamous cells [9]. In this study, A3G was found to participate in the interferon-alpha response and interferon-gamma response in SKCM patients, which might provide novel clues for SKCM treatments.…”

Section: Discussionmentioning

confidence: 56%

“…Furthermore, the dysregulation of A3G is also involved in multiple tumorigeneses. For example, Takashi Iizuka et al found that A3G is closely correlated with uterine cervical intraepithelial neoplasia (CIN) and might become an effective biomarker to assess CIN progression [9]. Also, A3G was observed to drive tumorigenesis in hepatocellular carcinoma (HCC) and might mediate host innate resistance to HBV infection and HCC [10].…”

Section: Ivyspringmentioning

confidence: 99%

Prognostic implication and functional annotations of APOBEC3G expression in patients with Melanoma

Han¹,

Xu²,

Shen³

2020

J. Cancer

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Aim: Skin cutaneous melanoma (SKCM) is one of the most life-threatening malignancies damaging human health. APOBEC3G (A3G) has been found in several cancers; however, the role of A3G in SKCM is rarely studied. This study aimed to investigate the expression of A3G in tumor tissue and its prognostic value in SKCM patients. Method: A total of 512 SKCM patients from the First Affiliated Hospital of Soochow University (FAHSU) and the Cancer Genome Atlas (TCGA) database were consecutively recruited in analyses. Differential transcriptional and proteome expression profiles were obtained from multiple datasets. GEPIA was used to assess the survival analysis between distinguished groups. Both univariate and multivariate Cox regression analysis was performed to address the influence of independent factors on disease-free survival (RFS) and overall survival (OS). In addition, 31 SKCM and 31 nevus tissues were collected for immunohistochemical (IHC) staining and evaluation. STRING, DAVID and Gene Set Enrichment Analysis (GSEA) was utilized to conduct a network of related genes and significant pathways. Furthermore, we investigated the relationship of A3G with tumor-infiltrating immune cells (TIICs) by TIMER and TISIDB. Result: We found both transcriptional and proteomics expressions of A3G were elevated in SKCM. Survival analysis and ROC curves showed significant diagnostic and prognostic ability of A3G. IHC results showed increased expression of A3G in SKCM compared to nevus tissues. Importantly, A3G expression was closely associated with the immune-infiltrating levels of B cells, CD4+ T, CD8+ T, neutrophils, macrophages and dendritic cells. Conclusion: In summary, our study first reveals that elevated A3G expression is significantly correlated with better prognosis in SKCM patients. The role of A3G in SKCM demonstrated that it might be a prognostic and immunotherapeutic biomarker for SKCM.

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APOBEC3G is increasingly expressed on the human uterine cervical intraepithelial neoplasia along with disease progression

Abstract: These findings indicate that A3G is associated with CIN, suggesting its important roles in human papillomavirus-induced pathophysiological processes such as CIN progression and viral elimination.

Cited by 15 publications

References 27 publications

Time Restriction of Food Intake During the Circadian Cycle Is a Possible Regulator of Reproductive Function in Postadolescent Female Rats

Time Restriction of Food Intake During the Circadian Cycle Is a Possible Regulator of Reproductive Function in Postadolescent Female Rats

APOBEC3B Activity Is Prevalent in Urothelial Carcinoma Cells and Only Slightly Affected by LINE-1 Expression

Prognostic implication and functional annotations of APOBEC3G expression in patients with Melanoma

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