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Overview of genetic and epigenetic regulation of human papillomavirus and apoptosis in cervical cancer

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A Correction to this article was published on 09 February 2023

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Abstract

Cervical cancer is the fourth most common cancer affecting women worldwide after breast, colorectal and lung cancers. Owing to a lack of awareness and resources, low- and middle-income countries bear most of the burden of cervical cancer. In developed countries, the incidence rate has been halved over the past three decades due to robust screening and implementation of vaccine programs. HPV is not the sole cause of cervical cancer but acts as a principal factor in the pathogenesis of cervical cancer. By integrating into the host genome, its oncogenic proteins (E6 and E7) alter and interfere with the standard signal transduction machinery of the host. Apoptosis is a key pathway affected by aberrant genetic mutations, polymorphisms and epigenetic mechanisms during cervical carcinogenesis. Along with DNA methylation and histone modifications, non-coding RNAs have also been implicated as epigenetic modulators in various malignancies and are being explored for reversing disease severity. This review emphasizes various genetic and epigenetic approaches regulating apoptotic pathways and HPV E6 and E7 genes that can be targeted to overcome the challenges in cervical cancer treatment. In addition, it also discusses the apoptosis targeting novel drug molecules in cervical cancer which are currently undergoing clinical and pre-clinical trials.

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Data availability

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Change history

Abbreviations

CC:

Cervical cancer

HPV:

Human papillomavirus

HR-HPV:

High risk human papillomavirus

LR-HPV:

Low risk human papillomavirus

CIN:

Cervical intraepithelial neoplasia

OC:

Oral contraceptive

STI:

Sexually transmitted infection

LCR:

Long control region

IRF:

Interferon regulatory factor

TSG:

Tumor suppressor gene

RAD51:

RAD51 recombinase

ETS2:

ETS proto-oncogene 2

TP63:

Tumor protein 63

KLF5:

Kruppel like factor 5

DR:

Death receptor

TNF:

Tumor necrosis factor

TRAIL:

TNF related apoptosis inducing ligand

FAS:

Fas cell surface death receptor

FADD:

FAS-associated death domain

DISC:

Death inducing signaling complex

CASPASE:

cysteine-aspartic proteases

RB:

retinoblastoma

MDM2:

Mouse double minute 2 homolog

STAT:

Signal transducer and activator of transcription

lncRNAs:

Long non-coding RNAs

mi-RNAs:

microRNAs

DAPK:

Death associated protein kinase

PEG3:

paternally-expressed gene 3

RASSF1:

Ras-associated domain family member 1

Bak:

Bcl-2 homologous antagonist

Bax:

Bcl-2 associated X

MEG3:

Maternally expressed 3

PKCSD:

Phosphoinositide 3- kinase catalytic subunit delta

PRKCD:

Protein kinase C delta polypeptide chain

MALAT1:

Metastasis associated lung adenocarcinoma transcript 1

HOTAIR:

HOX transcript antisense RNA

FIGO:

The International Federation of Gynaecology and Obstetrics

PTMs:

Post-translational modifications

HATs:

Histone acetyl transferases

HDACs:

Histone deacetyltransferases

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  1. Research Scholars, Department of Genetics, Maharshi Dayanand University, 124001, Rohtak, India

    Chetna Yadav, Ritu Yadav, Shalu Ranga & Parul Ahuja

  2. Department of Biochemistry, Central University of Punjab, 151401, Bathinda, Punjab, India

    Ravindresh Chabbra

  3. Department of Dermatology, Indiana University School of Medicine, 46202, Indianapolis, IN, USA

    Lokesh Kadian

  4. Department of Gynaecology and Obstetrics, Pt. B.D. Sharma University of Health Sciences, 124001, Rohtak, India

    Smiti Nanda

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Authors 1 and 2 designed the main draft of the manuscript text and wrote it. Author 1 drew the figure. Author 5 made Table 1. Authors 2 to 7 suggested reasonable changes, and authors 2 and 3 finalised the manuscript. Authors 1, 2, 3 and 5 did the revision.

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Yadav, C., Yadav, R., Chabbra, R. et al. Overview of genetic and epigenetic regulation of human papillomavirus and apoptosis in cervical cancer. Apoptosis 28, 683–701 (2023). https://doi.org/10.1007/s10495-023-01812-w

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