Integrated HPV genomes tend to integrate in gene desert areas in the CaSki, HeLa, and SiHa cervical cancer cell lines

Diao, Mingkun; Liu, Chuyi; Liu, Hongwei; Li, Jintao; Li, Fan; Mehryar, Mohammadreza Mohammadzad; Wang, Yangjunqi; Zhan, Shao-bing; Zhou, Yubai; Zhong, Rugang; Zeng, Yi

doi:10.1016/j.lfs.2015.01.039

Cited by 25 publications

(22 citation statements)

References 34 publications

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“…Besides HPV infection, alterations in cellular oncogenic events are also required for cervical cancer [63]. The integration of both HPV16 and HPV18 at the gene desert suggests that HPV coordinately affects oncogene alterations for cervical cancer formation [13,[64][65][66][67]. The integration hot spots in the gene desert include CASC8, CASC21, and POU5F1B [68,69].…”

Section: Association Of the 8q2421 Gene Desert With Oncogenesismentioning

confidence: 99%

The Oncogenic Potential of the Centromeric Border Protein FAM84B of the 8q24.21 Gene Desert

Lin

Kapoor

et al. 2020

Genes

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FAM84B is a risk gene in breast and prostate cancers. Its upregulation is associated with poor prognosis of prostate cancer, breast cancer, and esophageal squamous cell carcinoma. FAM84B facilitates cancer cell proliferation and invasion in vitro, and xenograft growth in vivo. The FAM84B and Myc genes border a 1.2 Mb gene desert at 8q24.21. Co-amplification of both occurs in 20 cancer types. Mice deficient of a 430 Kb fragment within the 1.2 Mb gene desert have downregulated FAM84B and Myc expressions concurrent with reduced breast cancer growth. Intriguingly, Myc works in partnership with other oncogenes, including Ras. FAM84B shares similarities with the H-Ras-like suppressor (HRASLS) family over their typical LRAT (lecithin:retinal acyltransferase) domain. This domain contains a catalytic triad, H23, H35, and C113, which constitutes the phospholipase A 1/2 and O-acyltransferase activities of HRASLS1-5. These enzymatic activities underlie their suppression of Ras. FAM84B conserves H23 and H35 but not C113 with both histidine residues residing within a highly conserved motif that FAM84B shares with HRASLS1-5. Deletion of this motif abolishes FAM84B oncogenic activities. These properties suggest a collaboration of FAM84B with Myc, consistent with the role of the gene desert in strengthening Myc functions. Here, we will discuss recent research on FAM84B-derived oncogenic potential.Genes 2020, 11, 312 2 of 15 non-coding RNA (lnRNA), and on its upstream or centromeric side sits a 1.2 Mb gene desert with the centromeric side bordered by the FAM84B or LRATD2 gene ( Figure 1). The unique feature of this gene desert is the existence of multiple (lnRNAs) (PCAT1, PCAT2, POU5F1B, CCAT1, CCAT2, CASC8, CASC11, CASC19, and CASC21) with FAM84B and Myc being the only protein coding genes (Figure 1) [12][13][14]. In view of Myc being the most-well-studied oncogene and the 8q24 gene desert as a region that is frequently amplified in cancer, FAM84B stands as a promising target for oncogenic activities; nonetheless, its impact on tumorigenesis remained unknown until recently. As the oncogenic potential of the non-coding RNAs of PVT1 and those within the gene desert (Figure 1) has been recently reviewed [13][14][15][16][17], we will focus on the emerging role of FAM84B in tumorigenesis in this review. We will briefly discuss the 8q24 gene desert with respect to oncogenesis to set the stage for the following systemic examination of the evidence pertinent to FAM84B-derived tumorigenesis. The main materials used in this review were chosen based on the PRISMA (preferred reporting items for systematic reviews and meta-analyses) Guidelines [18,19]. A literature search of the PubMed database for (1) "8q24 gene desert", revealed 28 papers with 6 irrelevant to tumorigenesis (Figure 2A) and (2) "FAM84B", identified 21 articles, including non-English papers (n = 1) and articles not directly related to FAM84B and cancer (n = 2) ( Figure 2B). After excluding these items, 22 articles on 8q24 gene desert and 18 papers related to the FAM84B topic h...

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Section: Association Of the 8q2421 Gene Desert With Oncogenesismentioning

confidence: 99%

The Oncogenic Potential of the Centromeric Border Protein FAM84B of the 8q24.21 Gene Desert

Lin

Kapoor

et al. 2020

Genes

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“…This study further provides evidence for the clinical treatment of cervical cancer by targeting TLR4-relevant molecules. [21]. For this study, the HeLa and CaSki cells were purchased from the Chinese Cell Bank (Shanghai, China).…”

Section: Introductionmentioning

confidence: 99%

The effect of TLR4 on the growth and local inflammatory microenvironment of HPV-related cervical cancer in vivo

Jiang

Xie

Chen

et al. 2020

Infect Agents Cancer

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Background: Cervical cancer is the most common malignancy of the female lower genital tract. In our previous study, we found that TLR4 promotes cervical cancer cell growth in vitro. The aim of this study was to further explore the role of TLR4 in HPV-related cervical cancer in vivo by using a nude mouse xenograft model. Methods: Cervical cancer-derived HeLa and CaSki cells (5 × 10 7 /mL) were either stimulated with an optimal concentration of LPS for the appropriate time (HeLa cells were treated with 1 μg/mL LPS for 1 h, and CaSki cells were treated with 2 μg/mL LPS for 1.5 h) or transfected with TLR4 shRNA and then injected subcutaneously into the dorsal right posterior side of nude mice. The shortest width and longest diameter of the transplanted tumors in the nude mice were measured every 3 days.TLR4, IL-6,iNOS, IL-8,COX-2, MIP-3α, TGF-β1 and VEGF expression levels in the transplanted tumor tissue were detected by immunohistochemistry. Results: The tumor formation rate was 100% in both HeLa and CaSki nude mouse groups. The tumors grew faster, and the cachexia symptoms were more serious in the LPS groups than in the control group. In contrast, the tumors grew slower, and the cachexia symptoms were milder in the TLR4-silenced groups. TLR4, iNOS, IL-6, MIP-3α and VEGF were highly expressed in the transplanted tumor tissues from the LPS groups, and their expression levels were decreased in the TLR4-silenced groups. Conclusion: TLR4 expression is closely associated with the tumorigenesis and growth of HPV-positive cervical cancer; TLR4 promotes HPV-positive cervical tumor growth and facilitates the formation of a local immunosuppressive microenvironment. Eventually, these conditions may lead to cervical cancer development.

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“…Cells. HPV + SiHa cells 24 were kindly provided by Dr. Berdasco Menendez from Bellvitge Biomedical Research Institute (IDIBELL, Spain). HaCaT cells (HPV16 negative) were obtained from Eucellbank (Banco de Células Eucariotas Celltech, UB).…”

Section: Methodsmentioning

confidence: 99%

“…The role of ADAR1 on HPV replication was evaluated in HPV16 + SiHa cells, containing the HPV genome integrated in chromosome 13q21 24 . HPV viral RNA and protein expression was measured in an ADAR1 loss-of-function cell model.…”

Section: Adar1 Regulates Hpv Expression In Siha Cell Linementioning

confidence: 99%

ADAR1 function affects HPV replication and is associated to recurrent human papillomavirus-induced dysplasia in HIV coinfected individuals

Pujantell¹,

Badía²,

Galván-Femenía³

et al. 2019

Sci Rep

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Infection by human papillomavirus (HPV) alters the microenvironment of keratinocytes as a mechanism to evade the immune system. A-to-I editing by ADAR1 has been reported to regulate innate immunity in response to viral infections. Here, we evaluated the role of ADAR1 in HPV infection in vitro and in vivo. Innate immune activation was characterized in human keratinocyte cell lines constitutively infected or not with HPV. ADAR1 knockdown induced an innate immune response through enhanced expression of RIG-I-like receptors (RLR) signaling cascade, over-production of type-I IFNs and pro-inflammatory cytokines. ADAR1 knockdown enhanced expression of HPV proteins, a process dependent on innate immune function as no A-to-I editing could be identified in HPV transcripts. A genetic association studywas performed in a cohort of HPV/HIV infected individuals followed for a median of 6 years (range 0.1-24). We identified the low frequency haplotype AACCAT significantly associated with recurrent HPV dysplasia, suggesting a role of ADAR1 in the outcome of HPV infection in HIV+ individuals. In summary, our results suggest that ADAR1-mediated innate immune activation may influence HPV disease outcome, therefore indicating that modification of innate immune effectors regulated by ADAR1 could be a therapeutic strategy against HPV infection.HPV is a small non-enveloped double-stranded DNA virus that infects keratinocytes. Most HPV infections clear spontaneously, however, persistent HPV infection is strongly associated with risk of several cancers including cervical, laryngeal, esophageal and anal cancer 1 . In immunosuppressed individuals there is a higher rate of cervical and anal HPV infections 2 . HPV infection favors HIV acquisition, and HIV-infected individuals encompass a heavier burden of HPV-induced dysplasia and cancer due to progressive immune suppression and impaired cell-mediated immunity. Persistent HPV infections are strong determinants of anal high-grade squamous intraepithelial lesions (HSIL) 3 .Innate immune responses are characterized by production of a complex network of cytokines that effectively activate cellular immune cells 4 . Pattern recognition receptors (PRRs) include the RNA-binding helicase family of RIG-I-like receptors (RLR: RIG-I and MDA5), and the family of Toll-like receptors (TLR). In response to viral infections, produced type I interferons (IFN) activate the Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway, which, in turn, induces the expression of additional interferon signaling

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Integrated HPV genomes tend to integrate in gene desert areas in the CaSki, HeLa, and SiHa cervical cancer cell lines

Cited by 25 publications

References 34 publications

The Oncogenic Potential of the Centromeric Border Protein FAM84B of the 8q24.21 Gene Desert

The Oncogenic Potential of the Centromeric Border Protein FAM84B of the 8q24.21 Gene Desert

The effect of TLR4 on the growth and local inflammatory microenvironment of HPV-related cervical cancer in vivo

ADAR1 function affects HPV replication and is associated to recurrent human papillomavirus-induced dysplasia in HIV coinfected individuals

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