Genetic analysis and allele-specific expression of SMAD7 3′UTR variants in human colorectal cancer reveal a novel somatic variant exhibiting allelic imbalance
Само за регистроване кориснике
2023
Аутори
Rosić, JovanaMiladinov, Marko
Dragičević, Sandra
Erić, Katarina
Bogdanović, Aleksandar
Krivokapić, Zoran
Nikolić, Aleksandra
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
Considering the impact of SMAD7 deregulation in colorectal cancer (CRC) progression and the
significance of single nucleotide variant (SNV)-mediated disruptions of microRNA (miRNA)-dependent regulation
for cancer susceptibility, our study aimed to analyze genetic variation in the SMAD7 3′ untranslated region (
3′UTR) in CRC, measure differences in allelic mRNA expression, and evaluate its interference with miRNAmediated
post-transcriptional regulation.
Patients and Methods: This study included 80 patients with different CRC stages and six human colon cancer cell
lines of various histological origins. SMAD7 3′ UTR was analyzed by direct sequencing, followed by the relative
quantification of differential allelic expression of detected variants by allele-specific qRT-PCR. In silico tools were
employed for predictions of regulatory consequences of detected variants.
Results: A total of four different SNVs in one cell line and nine patients were found, among which were a novel
som...atic point variant and three already known germline variants (rs16950113, rs1050799536, and
rs1043778717). All evaluated SNVs exhibited variable extents of allelic imbalance in expression. In silico analysis
predicted significant effects of SNVs on miRNA binding efficiency, with each SNV disrupting existing and
creating new target sites for one or more miRNAs.
Conclusion: Imbalance observed in the expression of SNV alleles altering miRNA binding suggests that all
investigated SNVs are potential contributing factors impacting SMAD7 expression regulation in CRC that further
studies should investigate.
Кључне речи:
colorectal cancer / SMAD7 / SNVs / 3′ UTR / allelic imbalance / miRNAИзвор:
Gene, 2023, 859, 147217-Издавач:
- Elsevier
Финансирање / пројекти:
- This work was supported by the strategic project of the Serbian Academy of Sciences and Arts (grant agreement No 02-2019) Molecular basis of response to chemioradiotherapy in rectal cancer - MOHERATEKA, F-69.
Колекције
Институција/група
Institut za molekularnu genetiku i genetičko inženjerstvoTY - JOUR AU - Rosić, Jovana AU - Miladinov, Marko AU - Dragičević, Sandra AU - Erić, Katarina AU - Bogdanović, Aleksandar AU - Krivokapić, Zoran AU - Nikolić, Aleksandra PY - 2023 UR - https://imagine.imgge.bg.ac.rs/handle/123456789/1769 AB - Considering the impact of SMAD7 deregulation in colorectal cancer (CRC) progression and the significance of single nucleotide variant (SNV)-mediated disruptions of microRNA (miRNA)-dependent regulation for cancer susceptibility, our study aimed to analyze genetic variation in the SMAD7 3′ untranslated region ( 3′UTR) in CRC, measure differences in allelic mRNA expression, and evaluate its interference with miRNAmediated post-transcriptional regulation. Patients and Methods: This study included 80 patients with different CRC stages and six human colon cancer cell lines of various histological origins. SMAD7 3′ UTR was analyzed by direct sequencing, followed by the relative quantification of differential allelic expression of detected variants by allele-specific qRT-PCR. In silico tools were employed for predictions of regulatory consequences of detected variants. Results: A total of four different SNVs in one cell line and nine patients were found, among which were a novel somatic point variant and three already known germline variants (rs16950113, rs1050799536, and rs1043778717). All evaluated SNVs exhibited variable extents of allelic imbalance in expression. In silico analysis predicted significant effects of SNVs on miRNA binding efficiency, with each SNV disrupting existing and creating new target sites for one or more miRNAs. Conclusion: Imbalance observed in the expression of SNV alleles altering miRNA binding suggests that all investigated SNVs are potential contributing factors impacting SMAD7 expression regulation in CRC that further studies should investigate. PB - Elsevier T2 - Gene T1 - Genetic analysis and allele-specific expression of SMAD7 3′UTR variants in human colorectal cancer reveal a novel somatic variant exhibiting allelic imbalance SP - 147217 VL - 859 DO - doi.org/10.1016/j.gene.2023.147217 ER -
@article{ author = "Rosić, Jovana and Miladinov, Marko and Dragičević, Sandra and Erić, Katarina and Bogdanović, Aleksandar and Krivokapić, Zoran and Nikolić, Aleksandra", year = "2023", abstract = "Considering the impact of SMAD7 deregulation in colorectal cancer (CRC) progression and the significance of single nucleotide variant (SNV)-mediated disruptions of microRNA (miRNA)-dependent regulation for cancer susceptibility, our study aimed to analyze genetic variation in the SMAD7 3′ untranslated region ( 3′UTR) in CRC, measure differences in allelic mRNA expression, and evaluate its interference with miRNAmediated post-transcriptional regulation. Patients and Methods: This study included 80 patients with different CRC stages and six human colon cancer cell lines of various histological origins. SMAD7 3′ UTR was analyzed by direct sequencing, followed by the relative quantification of differential allelic expression of detected variants by allele-specific qRT-PCR. In silico tools were employed for predictions of regulatory consequences of detected variants. Results: A total of four different SNVs in one cell line and nine patients were found, among which were a novel somatic point variant and three already known germline variants (rs16950113, rs1050799536, and rs1043778717). All evaluated SNVs exhibited variable extents of allelic imbalance in expression. In silico analysis predicted significant effects of SNVs on miRNA binding efficiency, with each SNV disrupting existing and creating new target sites for one or more miRNAs. Conclusion: Imbalance observed in the expression of SNV alleles altering miRNA binding suggests that all investigated SNVs are potential contributing factors impacting SMAD7 expression regulation in CRC that further studies should investigate.", publisher = "Elsevier", journal = "Gene", title = "Genetic analysis and allele-specific expression of SMAD7 3′UTR variants in human colorectal cancer reveal a novel somatic variant exhibiting allelic imbalance", pages = "147217", volume = "859", doi = "doi.org/10.1016/j.gene.2023.147217" }
Rosić, J., Miladinov, M., Dragičević, S., Erić, K., Bogdanović, A., Krivokapić, Z.,& Nikolić, A.. (2023). Genetic analysis and allele-specific expression of SMAD7 3′UTR variants in human colorectal cancer reveal a novel somatic variant exhibiting allelic imbalance. in Gene Elsevier., 859, 147217. https://doi.org/doi.org/10.1016/j.gene.2023.147217
Rosić J, Miladinov M, Dragičević S, Erić K, Bogdanović A, Krivokapić Z, Nikolić A. Genetic analysis and allele-specific expression of SMAD7 3′UTR variants in human colorectal cancer reveal a novel somatic variant exhibiting allelic imbalance. in Gene. 2023;859:147217. doi:doi.org/10.1016/j.gene.2023.147217 .
Rosić, Jovana, Miladinov, Marko, Dragičević, Sandra, Erić, Katarina, Bogdanović, Aleksandar, Krivokapić, Zoran, Nikolić, Aleksandra, "Genetic analysis and allele-specific expression of SMAD7 3′UTR variants in human colorectal cancer reveal a novel somatic variant exhibiting allelic imbalance" in Gene, 859 (2023):147217, https://doi.org/doi.org/10.1016/j.gene.2023.147217 . .