Structural Variations of the 3D Genome Architecture in Cervical Cancer Development

Human papillomavirus (HPV) integration is the major contributor to cervical cancer (CC) development by inducing structural variations (SVs) in the human genome. SVs are directly associated with the three-dimensional (3D) genome structure leading to cancer development. The detection of SVs is not a trivial task, and several genome-wide techniques have greatly helped in the identification of SVs in the cancerous genome. However, in cervical cancer, precise prediction of SVs mainly translocations and their effects on 3D-genome and gene expression still need to be explored. Here, we have used high-throughput chromosome conformation capture (Hi-C) data of cervical cancer to detect the SVs, especially the translocations, and validated it through whole-genome sequencing (WGS) data. We found that the cervical cancer 3D-genome architecture rearranges itself as compared to that in the normal tissue, and 24% of the total genome switches their A/B compartments. Moreover, translocation detection from Hi-C data showed the presence of high-resolution t(4;7) (q13.1; q31.32) and t(1;16) (q21.2; q22.1) translocations, which disrupted the expression of the genes located at and nearby positions. Enrichment analysis suggested that the disrupted genes were mainly involved in controlling cervical cancer-related pathways. In summary, we detect the novel SVs through Hi-C data and unfold the association among genome-reorganization, translocations, and gene expression regulation. The results help understand the underlying pathogenicity mechanism of SVs in cervical cancer development and identify the targeted therapeutics against cervical cancer.

Download Full-text

HPV16-LINC00393 Integration Alters Local 3D Genome Architecture in Cervical Cancer Cells

Frontiers in Cellular and Infection Microbiology ◽

10.3389/fcimb.2021.785169 ◽

2021 ◽

Vol 11 ◽

Author(s):

Xinxin Xu ◽

Zhiqiang Han ◽

Yetian Ruan ◽

Min Liu ◽

Guangxu Cao ◽

...

Keyword(s):

Cervical Cancer ◽

Cancer Cells ◽

Structural Changes ◽

Genome Structure ◽

Genomic Variation ◽

Chromosome Conformation ◽

3D Genome ◽

Cervical Cancer Cells ◽

Normal Human ◽

Cervical Cells

High-risk human papillomavirus (hrHPV) infection and integration were considered as essential onset factors for the development of cervical cancer. However, the mechanism on how hrHPV integration influences the host genome structure remains not fully understood. In this study, we performed in situ high-throughput chromosome conformation capture (Hi-C) sequencing, chromatin immunoprecipitation and sequencing (ChIP-seq), and RNA-sequencing (RNA-seq) in two cervical cells, 1) NHEK normal human epidermal keratinocyte; and 2) HPV16-integrated SiHa tumorigenic cervical cancer cells. Our results reveal that the HPV-LINC00393 integrated chromosome 13 exhibited significant genomic variation and differential gene expression, which was verified by calibrated CTCF and H3K27ac ChIP-Seq chromatin restructuring. Importantly, HPV16 integration led to differential responses in topologically associated domain (TAD) boundaries, with a decrease in the tumor suppressor KLF12 expression downstream of LINC00393. Overall, this study provides significant insight into the understanding of HPV16 integration induced 3D structural changes and their contributions on tumorigenesis, which supplements the theory basis for the cervical carcinogenic mechanism of HPV16 integration.

Download Full-text

Cervical cancer development, chemoresistance, and therapy: a snapshot of involvement of microRNA

Molecular and Cellular Biochemistry ◽

10.1007/s11010-021-04249-4 ◽

2021 ◽

Author(s):

Tandrima Mitra ◽

Selvakumar Elangovan

Keyword(s):

Cervical Cancer ◽

Cancer Development ◽

Cervical Cancer Development

Download Full-text

miR-122 Inhibits the Cervical Cancer Development by Targeting the Oncogene RAD21

Biochemical Genetics ◽

10.1007/s10528-021-10098-z ◽

2021 ◽

Author(s):

Yanling Yang ◽

Yang Liu ◽

Wei Liu ◽

Chunyang Li ◽

Yuan Liu ◽

...

Keyword(s):

Cervical Cancer ◽

Cancer Development ◽

Cervical Cancer Development

Download Full-text

Role of inflammasome genetics in susceptibility to HPV infection and cervical cancer development

Journal of Medical Virology ◽

10.1002/jmv.24514 ◽

2016 ◽

Vol 88 (9) ◽

pp. 1646-1651 ◽

Cited By ~ 28

Author(s):

A. Pontillo ◽

P. Bricher ◽

V.N.C. Leal ◽

S. Lima ◽

P.R.E. Souza ◽

...

Keyword(s):

Cervical Cancer ◽

Hpv Infection ◽

Cancer Development ◽

Cervical Cancer Development

Download Full-text

3D genome structure reconstruction from chromosomal contact data

10.32469/10355/67541 ◽

2017 ◽

Author(s):

◽

Tuan Anh Trieu

Keyword(s):

High Resolution ◽

Genome Structure ◽

Cell Types ◽

3D Models ◽

Graphic User Interface ◽

Soft Constraints ◽

Chromosome Conformation ◽

3D Genome ◽

Manual Adjustment ◽

The Relationship

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] Different cell types of an organism have the same DNA sequence, but they can function differently because their difference in 3D organization allows them to express different genes and has different cellular functions. Understanding the 3D organization of the genome is the key to understand functions of the cell. Chromosome conformation capture techniques like Hi-C and TCC that can capture interactions between proximal chromosome fragments have allowed the study of 3D genome organization in high resolution and high through-put. My work focuses on developing computational methods to reconstruct 3D genome structures from Hi-C data. I presented three methods to reconstruct 3D genome and chromosome structures. The first method can build 3D genome models from soft constraints of contacts and non-contacts. This method utilizes the concept of contact and non-contact to reconstruct 3D models without translating interaction frequencies into physical distances. The translation is commonly used by other methods even though it makes a strong assumption about the relationship between interaction frequencies and physical distances. In synthetic dataset, when the relationship was known, my method performed comparably with other methods assuming the relationship. This shows the potential of my method for real Hi-C datasets where the relationship is unknown. The limitation of the method is that it has parameters requiring manual adjustment. I developed the second method to reconstruct 3D genome models. This method utilizes a commonly used function to translate interaction frequencies to physical distances to build 3D models. I proposed a novel way to derive soft constraints to handle inconsistency in the data and to make the method robust. Building 3D models at high resolution is a more challenging problem as the number of constraints is small and the feasible space is larger. I introduced a third method to build 3D chromosome models at high resolution. The method reconstructs models at low resolution and then uses them to guide the reconstruction of models at high resolution. The last part of my work is the development of a comprehensive tool with intuitive graphic user interface to analyze Hi-C data, reconstruct and analyze 3D models.

Download Full-text

Genetic polymorphisms and cervical cancer development: ATM G5557A and p53bp1 C1236G

Oncology Reports ◽

10.3892/or.2011.1609 ◽

2011 ◽

Vol 27 (4) ◽

pp. 1188-1192 ◽

Cited By ~ 14

Author(s):

S. OLIVEIRA ◽

J. RIBEIRO ◽

H. SOUSA ◽

D. PINTO ◽

I. BALDAQUE ◽

...

Keyword(s):

Cervical Cancer ◽

Genetic Polymorphisms ◽

Cancer Development ◽

Cervical Cancer Development

Download Full-text

Human Papillomavirus 16 Oncoproteins Downregulate the Expression of miR-148a-3p, miR-190a-5p, and miR-199b-5p in Cervical Cancer

BioMed Research International ◽

10.1155/2018/1942867 ◽

2018 ◽

Vol 2018 ◽

pp. 1-9 ◽

Cited By ~ 5

Author(s):

Mi-Soon Han ◽

Jae Myun Lee ◽

Soo-Nyung Kim ◽

Jae-Hoon Kim ◽

Hyon-Suk Kim

Keyword(s):

Cervical Cancer ◽

Human Papillomavirus ◽

High Risk ◽

Expression Profiles ◽

Normal Group ◽

Cancer Development ◽

Hybridization Method ◽

Cancer Group ◽

Cervical Cancer Development ◽

High Risk Hpv

Almost all cervical cancers are associated with human papillomavirus (HPV); however, the majority of women infected with this virus do not develop cervical cancer. Therefore, new markers are needed for reliable screening of cervical cancer, especially in relation to HPV infection. We aimed to identify potential microRNAs that may serve as diagnostic markers for cervical cancer development in high-risk HPV-positive patients. We evaluated the microRNA expression profiles in 12 cervical tissues using the hybridization method and verified them by quantitative polymerase chain reaction (qPCR). Finally, we evaluated the effects of HPV16 oncoproteins on the expression of selected microRNAs using cervical cancer cells (CaSki and SiHa) and RNA interference. With the hybridization method, eight microRNAs (miR-9-5p, miR-136-5p, miR-148a-3p, miR-190a-5p, miR-199b-5p, miR-382-5p, miR-597-5p, and miR-655-3p) were found to be expressed differently in the HPV16-positive cervical cancer group and HPV16-positive normal group (fold change ≥ 2). The results of qPCR showed that miR-148a-3p, miR-190a-5p, miR-199b-5p, and miR-655-3p levels significantly decreased in the cancer group compared with the normal group. Upon silencing of HPV16 E5 and E6/E7, miR-148a-3p levels increased in both cell lines. Silencing of E6/E7 in SiHa cells led to the increase in miR-199b-5p and miR-190a-5p levels. Three HPV16 oncoproteins (E5, E6, and E7) downregulate miR-148a-3p, while E6/E7 inhibit miR-199b-5p and miR-190a-5p expression in cervical carcinoma. The three microRNAs, miR-148a-3p, miR-199b-5p, and miR-190a-5p, may be novel diagnostic biomarkers for cervical cancer development in high-risk HPV-positive patients.

Download Full-text

SMAD2 rs4940086 heterozygosity increases the risk of cervical cancer development among the women in Bangladesh

Molecular Biology Reports ◽

10.1007/s11033-020-05572-7 ◽

2020 ◽

Vol 47 (7) ◽

pp. 5033-5040

Author(s):

Parsa Sanjana Haque ◽

Mohd Nazmul Hasan Apu ◽

Noor Ahmed Nahid ◽

Farhana Islam ◽

Md Reazul Islam ◽

...

Keyword(s):

Cervical Cancer ◽

Cancer Development ◽

Cervical Cancer Development

Download Full-text

From Microbiome to Inflammation: The Key Drivers of Cervical Cancer

Frontiers in Microbiology ◽

10.3389/fmicb.2021.767931 ◽

2021 ◽

Vol 12 ◽

Author(s):

Zi-Wei Zhou ◽

Hui-Zhi Long ◽

Yan Cheng ◽

Hong-Yu Luo ◽

Dan-Dan Wen ◽

...

Keyword(s):

Cervical Cancer ◽

Cancer Development ◽

The Third ◽

Host Body ◽

Key Drivers ◽

Cervical Cancer Development ◽

The Relationship

Cervical cancer is the third leading cause of cancer-related death worldwide. Microbes and hosts form a mutually beneficial symbiosis relationship, and various parts of the host body are microbial habitats. Microbes can trigger inflammation in certain parts of the host body, contributing to cervical cancer development. This article reviews the relationship between cervicovaginal microbes, inflammation and cervical cancer, and discusses the effect of some key cervical microbes on cervical cancer. Finally, probiotic therapy and immunotherapy are summarized.

Download Full-text