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Promising candidate drug target genes for repurposing in cervical cancer: A bioinformatics-based approach Pratiwi, Nurfi; Ulfah, Aida J.; Rachmadina, Rachmadina; Irham, Lalu M.; Afief, Arief R.; Adikusuma, Wirawan; Darmawi, Darmawi; Kemal, Rahmat A.; Rangkuti, Ina F.; Savira, Maya
Narra J Vol. 4 No. 3 (2024): December 2024
Publisher : Narra Sains Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.52225/narra.v4i3.938

Abstract

Cervical cancer is the fourth most common cancer among women globally, and studies have shown that genetic variants play a significant role in its development. A variety of germline and somatic mutations are associated with cervical cancer. However, genomic data derived from these mutations have not been extensively utilized for the development of repurposed drugs for cervical cancer. The objective of this study was to identify novel potential drugs that could be repurposed for cervical cancer treatment through a bioinformatics approach. A comprehensive genomic and bioinformatics database integration strategy was employed to identify potential drug target genes for cervical cancer. Using the GWAS and PheWAS databases, a total of 232 genes associated with cervical cancer were identified. These pharmacological target genes were further refined by applying a biological threshold of six functional annotations. The drug target genes were then cross-referenced with cancer treatment candidates using the DrugBank database. Among the identified genes, LTA, TNFRSF1A, PRKCZ, PDE4B, and PARP were highlighted as promising targets for repurposed drugs. Notably, these five target genes overlapped with 12 drugs that could potentially be repurposed for cervical cancer treatment. Among these, talazoparib, a potent PARP inhibitor, emerged as a particularly promising candidate. Talazoparib is currently being investigated for safety and tolerability in other cancers but has not yet been studied in the context of cervical cancer. Further clinical trials are necessary to validate this finding and explore its potential as a repurposed drug for cervical cancer.
Genetic variations of the L2 gene in human papillomavirus (HPV) type 16 from cervical cancer patients in Sumatra region, Indonesia Savira, Maya; Farniga, Arnaldi; Ilmiah, Zidny; Rachmadina, Rachmadina; Rini, Ika A.; Kemal, Rahmat A.; Mahargyarani, Azza E.; Admiral, Muhammad Z.; Sofian, Amru; Razali, Renardy R.; Suhaimi, Donel; Putra, Andani E.
Narra J Vol. 5 No. 2 (2025): August 2025
Publisher : Narra Sains Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.52225/narra.v5i2.1653

Abstract

The L2 protein, a minor capsid component of human papillomavirus (HPV), plays a critical role in the HPV life cycle by packaging the viral genome with the L1 protein and facilitating DNA transport to the nucleus. Identifying genetic variations in the L2 gene is essential for improving vaccine development, diagnostic accuracy, and understanding viral evolution, potentially contributing to more effective HPV vaccines. The aim of this study was to investigate the genetic variation of the L2 gene in cervical cancer specimens collected from patients in Riau Province, Indonesia. A single-center, cross-sectional study was conducted at Arifin Achmad General Hospital, Riau Province, involving cervical cancer patients with confirmed HPV16 infection between January 2018 and August 2020. Demographic, clinical, and risk factor data were collected through structured interviews and direct assessments. Cervical biopsy specimens were collected, and viral DNA was extracted for L2 gene amplification using polymerase chain reaction (PCR). Sequencing was conducted on PCR products, followed by single-nucleotide polymorphism (SNP) identification through alignment with the HPV16 reference genome. The amplification and sequencing of the HPV16 L2 gene from 22 cervical cancer specimens revealed 36 SNPs, including 31 nonsynonymous and five synonymous mutations. High-frequency mutations were observed at nucleotide positions 4,074 and 4,177, each detected in 95.45% of the samples. Notable insertions were found at positions 3,668–3,669 and 4,275–4,276, indicating substantial sequence variation. Phylogenetic analysis grouped the sequences into three clusters, with most belonging to sub-lineage A2 (European), while others aligned with A4 (Asian) and East Asian lineages. The observed genetic diversity in the HPV16 L2 gene may reflect regional viral evolution and has potential implications for future vaccine development.
Genetic diversity in the E6 and E7 gene of human papillomavirus type 16 among cervical cancer patients in Riau Province, Indonesia Savira, Maya; Rachmadina, Rachmadina; Mahargyarani, Azza Enggar; Admiral, Muhammad Zhafran; S, Donel; Sofian, Amru; Razali, Renady Reza; Ilmiah, Zidny; Farniga, Analdi
JURNAL INDONESIA DARI ILMU LABORATORIUM MEDIS DAN TEKNOLOGI Vol 8 No 1 (2026): Integration of Molecular Approaches in Addressing Drug Resistance and Changing Gl
Publisher : Universitas Nahdlatul Ulama Surabaya

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.33086/ijmlst.v8i1.6652

Abstract

Cervical cancer mostly occurs due to persistent high-risk human papillomavirus (HPV), with type 16 being the most frequent. In Indonesia, cervical cancer ranks second in mortality, with a fatality rate of 57%. The E6 and E7 genes of HPV-16 play crucial roles in the virus’s oncogenic transformation, leading to cervical cancer. This study was conducted to determine the prevalence and genetic diversity of the E6 and E7 genes of HPV-16 in Riau Province, Indonesia. There were 37 HPV-positive samples analyzed using the MY09/11 primers. This was followed by the amplification of the E6 and E7 genes. Nineteen samples were detected as HPV-16, thirteen of which were coinfected with HPV-18. Seven E6 and E7 sequences were aligned compared with the reference sequence NC_001526.4. The most common nucleotide changes in the E6 gene, 7318A>G, was detected in 30.7% of samples, leading to an amino acid change from 65N>S. Three nucleotide changes were identified in the E7 gene of sample 89: two synonymous (7831T>C, 7837T>G) and one non-synonymous (7989A>G), resulting in an amino acid change of 29N>S. The most frequent E7 nucleotide change, 7708G>A, was found in 80% of samples. Phylogenetic analysis revealed that HPV-16 isolates from Riau have close kinship with the European lineage, with 57.1% (E6) and 85.7% (E7). In conclusion, the incidence of cervical cancer in Riau Province caused by HPV-16 is 52.8% and 7318A>G and 7708G>A are the most common genetic diversity. Furthermore, the majority of HPV-16 isolates in Riau Province show close kinship with the European lineage.