Analysis of transcripts from alternative PRKAR1B gene promoters in colorectal cancer
Apstrakt
Background/Objectives: The transcriptional regulation of
PRKAR1B is controlled by alternative promoters, and previous in
silico analysis has indicated their differential activity in colon and
rectal cancer tissue in comparison to normal gut mucosa. The aim
of this study was to investigate PRKAR1B promoters and transcripts
potentially involved in cancer.
Methods: The sequences of PRKAR1B alternative promoters
were retrieved from Ensembl database: promoter A 752209 and
promoter B 767287 bases upstream from the translation start site.
Bioinformatic tools Alggen, AliBaba, CiiiDER, and TFBIND were
used to predict binding of transcriptional regulators. Primer
extension assay was performed on RNA isolated from malignant
colon cell lines using an oligonucleotide probe binding to the
sequence at the exon2/exon3 junction common for all PRKAR1B
transcripts.
Results: Based on analyzed elements, both PRKAR1B promoters
were found to have atypical structure. According to the predictio...n,
promoter A that encodes transcript PRKAR1B-201 binds several
factors involved in cell proliferation, while promoter B that encodes
transcript PRKAR1B-203 binds mostly pro-apoptotic factors. In primer
extension experiments, a single signal corresponding to the
transcript PRKAR1B-212 was observed in malignant cells.
Conclusion: The differential activity of alternative PRKAR1B
promoters in colorectal cancer can be explained by in silico
results, predicting that promoter sequences bind sets of transcriptional
regulators with opposing roles. However, experiments
point to the transcript unrelated to either of the investigated
promoters as potential cancer biomarker and it should be further
characterized.
Ključne reči:
colorectal cancer / alternative promoters / PRKAR1B / alternative transcriptsIzvor:
European Journal of Human Genetic, 2023, 31, Supplement S1, 249-249Izdavač:
- Springer Nature
Finansiranje / projekti:
- SENSOGENE - Cancer Biosensors Based on Gene Regulatory Elements (RS-ScienceFundRS-Promis-6052315)
Napomena:
- Abstracts from the 55th European Society of Human Genetics (ESHG) Conference: e-Posters; Vienna, Austria. June 11–14, 2022
URI
https://www.nature.com/articles/s41431-023-01339-3#Sec859https://imagine.imgge.bg.ac.rs/handle/123456789/1973
Institucija/grupa
Institut za molekularnu genetiku i genetičko inženjerstvoTY - CONF AU - Pavlović, Dunja AU - Babić, Tamara AU - Nikolić, Aleksandra PY - 2023 UR - https://www.nature.com/articles/s41431-023-01339-3#Sec859 UR - https://imagine.imgge.bg.ac.rs/handle/123456789/1973 AB - Background/Objectives: The transcriptional regulation of PRKAR1B is controlled by alternative promoters, and previous in silico analysis has indicated their differential activity in colon and rectal cancer tissue in comparison to normal gut mucosa. The aim of this study was to investigate PRKAR1B promoters and transcripts potentially involved in cancer. Methods: The sequences of PRKAR1B alternative promoters were retrieved from Ensembl database: promoter A 752209 and promoter B 767287 bases upstream from the translation start site. Bioinformatic tools Alggen, AliBaba, CiiiDER, and TFBIND were used to predict binding of transcriptional regulators. Primer extension assay was performed on RNA isolated from malignant colon cell lines using an oligonucleotide probe binding to the sequence at the exon2/exon3 junction common for all PRKAR1B transcripts. Results: Based on analyzed elements, both PRKAR1B promoters were found to have atypical structure. According to the prediction, promoter A that encodes transcript PRKAR1B-201 binds several factors involved in cell proliferation, while promoter B that encodes transcript PRKAR1B-203 binds mostly pro-apoptotic factors. In primer extension experiments, a single signal corresponding to the transcript PRKAR1B-212 was observed in malignant cells. Conclusion: The differential activity of alternative PRKAR1B promoters in colorectal cancer can be explained by in silico results, predicting that promoter sequences bind sets of transcriptional regulators with opposing roles. However, experiments point to the transcript unrelated to either of the investigated promoters as potential cancer biomarker and it should be further characterized. PB - Springer Nature C3 - European Journal of Human Genetic T1 - Analysis of transcripts from alternative PRKAR1B gene promoters in colorectal cancer EP - 249 IS - Supplement S1 SP - 249 VL - 31 UR - https://hdl.handle.net/21.15107/rcub_imagine_1973 ER -
@conference{ author = "Pavlović, Dunja and Babić, Tamara and Nikolić, Aleksandra", year = "2023", abstract = "Background/Objectives: The transcriptional regulation of PRKAR1B is controlled by alternative promoters, and previous in silico analysis has indicated their differential activity in colon and rectal cancer tissue in comparison to normal gut mucosa. The aim of this study was to investigate PRKAR1B promoters and transcripts potentially involved in cancer. Methods: The sequences of PRKAR1B alternative promoters were retrieved from Ensembl database: promoter A 752209 and promoter B 767287 bases upstream from the translation start site. Bioinformatic tools Alggen, AliBaba, CiiiDER, and TFBIND were used to predict binding of transcriptional regulators. Primer extension assay was performed on RNA isolated from malignant colon cell lines using an oligonucleotide probe binding to the sequence at the exon2/exon3 junction common for all PRKAR1B transcripts. Results: Based on analyzed elements, both PRKAR1B promoters were found to have atypical structure. According to the prediction, promoter A that encodes transcript PRKAR1B-201 binds several factors involved in cell proliferation, while promoter B that encodes transcript PRKAR1B-203 binds mostly pro-apoptotic factors. In primer extension experiments, a single signal corresponding to the transcript PRKAR1B-212 was observed in malignant cells. Conclusion: The differential activity of alternative PRKAR1B promoters in colorectal cancer can be explained by in silico results, predicting that promoter sequences bind sets of transcriptional regulators with opposing roles. However, experiments point to the transcript unrelated to either of the investigated promoters as potential cancer biomarker and it should be further characterized.", publisher = "Springer Nature", journal = "European Journal of Human Genetic", title = "Analysis of transcripts from alternative PRKAR1B gene promoters in colorectal cancer", pages = "249-249", number = "Supplement S1", volume = "31", url = "https://hdl.handle.net/21.15107/rcub_imagine_1973" }
Pavlović, D., Babić, T.,& Nikolić, A.. (2023). Analysis of transcripts from alternative PRKAR1B gene promoters in colorectal cancer. in European Journal of Human Genetic Springer Nature., 31(Supplement S1), 249-249. https://hdl.handle.net/21.15107/rcub_imagine_1973
Pavlović D, Babić T, Nikolić A. Analysis of transcripts from alternative PRKAR1B gene promoters in colorectal cancer. in European Journal of Human Genetic. 2023;31(Supplement S1):249-249. https://hdl.handle.net/21.15107/rcub_imagine_1973 .
Pavlović, Dunja, Babić, Tamara, Nikolić, Aleksandra, "Analysis of transcripts from alternative PRKAR1B gene promoters in colorectal cancer" in European Journal of Human Genetic, 31, no. Supplement S1 (2023):249-249, https://hdl.handle.net/21.15107/rcub_imagine_1973 .