Characteristic of HPV Integration in the Genome and Transcriptome of Cervical Cancer Tissues

Li, Weiyang; Qi, Yanwei; Cui, Xiaofang; Huo, Qing; Zhu, Li; Zhang, Aiping; Tan, Meihua; Hong, Qilan; Yang, Yan; Zhang, Huali; Liu, Chuanxin; Kong, Qingsheng; Geng, Jiazheng; Tian, Yuan; Kong, Fancong; Man, Dongmei

doi:10.1155/2018/6242173

Cited by 42 publications

(43 citation statements)

References 23 publications

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“…For 40 specimens, the retrospective results of HPV type detection were given by commercial HPV type detection kits, which was approved by CFDA, and the detection method was FHGC. In the retrospective results, the HPV subtypes were mainly HPV16 and HPV18; the HPV multiple infection ratio was 35% (14/40), which was exactly consistent with the previous reports [17]. But Tau-protein kinase activity 2 2 2 3 6 Figure 6: GO categories assigned to all 6867 integration genes.…”

Section: Discussionsupporting

confidence: 88%

“…In their report, POU5F1B, FHIT, KLF12, HMGA2, KLF5, LRP1B, LEPREL1, DLG2, and SEMA3D were the hotspots. But the highfrequency integration sites reported by Li et al were FHIT, CASC8, KLF5, LINC00392, RAD51B, CASC21, ERBB2, TP63, TEX41, RAP2B, and MYC [17]. These highfrequency integration sites were quite different, which indicates that there were different high-frequency integration sites in different sample sources.…”

Section: Discussionmentioning

confidence: 88%

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Genome-Wide Profiling of Human Papillomavirus DNA Integration into Human Genome and Its Influence on PD-L1 Expression in Chinese Uygur Cervical Cancer Women

Feng

Sen-Yu

Yuan

et al. 2020

Journal of Immunology Research

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Background. The Uygur is the fifth most populous ethnic group in China. Compared to other Chinese population, cervical cancer in them had high incidence, and HPV infection also was particular. Their HPV integration situation has never been reported. We aimed to investigate the integration situation of 20 subtypes of HPV gene into host cell genome in Chinese Uygur cervical cancer patients; meanwhile, we explored the influence of gene integration on PD-L1 expression. Methods. 40 frozen Chinese Uygur cervical cancer specimens with positive HPV infection were obtained from the cancer prevention and treatment institute of Tumor Hospital Affiliated to Xinjiang Medical University. The integration situation of HPV gene into host cell genome was detected by Agilent SureSelect™ Target Enrichment Chip and Next-Generation Sequencing. The related genes were analyzed by GO functional annotation and KEGG pathway enrichment. The expression levels of PD-L1 in cancer cells were tested by immunohistochemical assay (IHC). Meanwhile, the relationship between PD-L1 levels in cancer cells and gene integration were analyzed. Results. The HPV multiple infection rate by HIVID was as high as 92.5%, much higher than 35.0% by the commercial kit (P<0.05). There were 13423 integration events in 40 specimens, involving 6867 human genes. These integration events were distributed on all human chromosomes, and chromosome 19 had the excessive concentration phenomenon of integration events. There were some integration hotspots in human genome such as PPP1R37, HECW2, EMBP1, ANKRD50, SPTBN4, LINC00895, LYRM4-AS1, LINC00374, RBFOX1, CSMD1, CDH13, and KLHL4. Insertion breakpoints can be found in all gene regions of the HPV genome. The actual observation of the integration times of E1 and E6 was much higher than the expected value, while the actual observation times of E5 were much lower than the expected value. The result of GO functional analysis showed that binding molecular function and cellular process biological process were the main ways to influence the cell biological behavior of HPV gene integration. The enrichment pathway analysis of KEGG showed that pathways in cancer were the most important enrichment pathways involved in the genomic integration of HPV. The positive PD-L1 rate was 62.5%. Logistic regression analysis showed that 9p24.1 existing integration sites and the number of all gene integration were risk factors for PD-L1 expression (odds ratio 17.313 and 1.012; 95% confidence interval 1.691-177.213 and 1.001-1.023). Conclusions and Relevance. Most high-frequency sites of HPV integration in Chinese Uygur cervical cancer are related to cancer progression, and the gene integration hotspots may be potential HPV carcinogenic targets. The problem of multiple HPV infection in Chinese Uygur cervical cancer patients should be paid attention. L1 and E6 genes are inapposite as the target gene of commercial HPV type detection kit, because of high-frequency breakpoints in these genes. The gene integration especially the integration existing on 9p24.1 could affect the expression level of PD-L1.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 88%

Genome-Wide Profiling of Human Papillomavirus DNA Integration into Human Genome and Its Influence on PD-L1 Expression in Chinese Uygur Cervical Cancer Women

Feng

Sen-Yu

Yuan

et al. 2020

Journal of Immunology Research

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“…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]. Among 3667 breakpoints of HPV integration detected in cervical carcinoma (n = 104), cervical intraepithelial neoplasia (n = 26), and 5 cervical cancer cell lines, POU5F1B is the top site of integration (9.7%) [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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“…There are very few studies on it at present. Li et al reported that CASC21 was a hotspot gene integrated by HPV in cervical cancer [31]. Interestingly, Zheng et al also found that CASC21 played an oncogenic role in CRC.…”

Section: Discussionmentioning

confidence: 99%

CASC21, a FOXP1 induced long non-coding RNA, promotes colorectal cancer growth by regulating CDK6

Gong

Feng

et al. 2020

Aging

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Emerging studies indicate that long non-coding RNAs (lncRNAs) play crucial roles in colorectal cancer (CRC). Here, we reported lncRNA CASC21, which is induced by FOXP1, functions as an oncogene in CRC. We systematically elucidated its clinical significance and possible molecular mechanism in CRC. LncRNA expression in CRC was analyzed by RNA-sequencing data in TCGA. The expression level of CASC21 in tissues was determined by qRT-PCR. The functions of CASC21 was investigated by in vitro and in vivo assays (CCK8 assay, colony formation assay, EdU assay, xenograft model, flow cytometry assay, immunohistochemistry (IHC) and Western blot). Chromatin immunoprecipitation (ChIP), RNA immunoprecipitation (RIP) and luciferase reporter assays were utilized to demonstrate the potential mechanisms of CASC21. CASC21 is overexpressed in CRC and high CASC21 expression is associated with poor survival. Functional experiments revealed that CASC21 promotes CRC cell growth. Mechanistically, we found that CASC21 expressed predominantly in the cytoplasm. CASC21 could interact with miR-539-5p and regulate its target CDK6. Together, our study elucidated that CASC21 acted as an oncogene in CRC, which might serve as a novel target for CRC diagnosis and therapy.

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Characteristic of HPV Integration in the Genome and Transcriptome of Cervical Cancer Tissues

Cited by 42 publications

References 23 publications

Genome-Wide Profiling of Human Papillomavirus DNA Integration into Human Genome and Its Influence on PD-L1 Expression in Chinese Uygur Cervical Cancer Women

Genome-Wide Profiling of Human Papillomavirus DNA Integration into Human Genome and Its Influence on PD-L1 Expression in Chinese Uygur Cervical Cancer Women

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

CASC21, a FOXP1 induced long non-coding RNA, promotes colorectal cancer growth by regulating CDK6

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