Analysis of Alternative LDLRAD4 Gene Promoters and Transcripts in Colorectal Cancer
2022
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Конференцијски прилог (Објављена верзија)
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Gene LDLRAD4 plays a role in cell proliferation, apoptosis, immunosuppression and cancer
progression. Transcription of LDLRAD4 is regulated by several alternative promoters, two of which
were indicated by in silico analyses to be differentially active in rectal cancer. Promoter A encodes for a
truncated protein-coding transcript and is down-regulated in rectal cancer. Promoter B encodes for a
non-coding transcript up-regulated in rectal cancer identified as lnc-RNMT-2:5. The aim of this study
was to characterize the two alternative promoters in silico in order to explain their differential activity
and to investigate the profile of LDLRAD4 transcripts in colon cell lines. Nucleotide sequences used in
the analyses were downloaded from the Ensemble genome database (reference GRCh37). Three
bioinformatics tools were used for core promoter element prediction: GPMiner, YAPP and
CNNPromoter. Four bioinformatics tools were used for transcription factor binding site prediction:
PROMO..., TFBIND, CiiiDER and Tfsitescan. Only the predictions made by two or more tools were
considered. Primer extension followed by fragment analysis was used to characterize LDLRAD4
transcripts present in colon cell lines. The promoter element predictions showed that the promoter A is
typical, while promoter B has most typical elements and lacks GC boxes. The transcription binding site
predictions indicate that three different transcription factors bind only to the promoter A (NF-kB,
EGR1 and IRF-7), while four different transcription factors bind only to the promoter B (HNF1,
POU2F1, POU2F2 and PTF1). The predicted transcription factors are mostly involved in regulation of
cell differentiation and proliferation. The primer extension experiment performed with primer specific
for exon 2-exon 3 junction produced multiple signals of relatively low intensity, indicating the presence
of multiple LDLRAD4 transcripts in colon cell lines. The results obtained by in silico analysis may
explain promoter B activation in rectal cancer. However, based on the results of primer extension, neither
of the LDLRAD4 transcripts is dominant in colon cell lines. Considering that promoter B generates
long non-coding RNA that can exert its function even at low expression level, it can serve as potential
colorectal cancer biomarker and its potential role in carcinogenesis should be investigated.
Извор:
“HDIR-6: Targeting Cancer” The 6th Meeting of the Croatian Association for Cancer Research with International Participation – Book of Abstracts, 2022, 35-35Издавач:
- Croatian Association for Cancer Research, Zagreb, Croatia
Финансирање / пројекти:
- SENSOGENE - Cancer Biosensors Based on Gene Regulatory Elements (RS-ScienceFundRS-Promis-6052315)
Институција/група
Institut za molekularnu genetiku i genetičko inženjerstvoTY - CONF AU - Velimirov, Luka AU - Babić, Tamara AU - Dragičević, Sandra AU - Nikolić, Aleksandra PY - 2022 UR - https://imagine.imgge.bg.ac.rs/handle/123456789/2084 AB - Gene LDLRAD4 plays a role in cell proliferation, apoptosis, immunosuppression and cancer progression. Transcription of LDLRAD4 is regulated by several alternative promoters, two of which were indicated by in silico analyses to be differentially active in rectal cancer. Promoter A encodes for a truncated protein-coding transcript and is down-regulated in rectal cancer. Promoter B encodes for a non-coding transcript up-regulated in rectal cancer identified as lnc-RNMT-2:5. The aim of this study was to characterize the two alternative promoters in silico in order to explain their differential activity and to investigate the profile of LDLRAD4 transcripts in colon cell lines. Nucleotide sequences used in the analyses were downloaded from the Ensemble genome database (reference GRCh37). Three bioinformatics tools were used for core promoter element prediction: GPMiner, YAPP and CNNPromoter. Four bioinformatics tools were used for transcription factor binding site prediction: PROMO, TFBIND, CiiiDER and Tfsitescan. Only the predictions made by two or more tools were considered. Primer extension followed by fragment analysis was used to characterize LDLRAD4 transcripts present in colon cell lines. The promoter element predictions showed that the promoter A is typical, while promoter B has most typical elements and lacks GC boxes. The transcription binding site predictions indicate that three different transcription factors bind only to the promoter A (NF-kB, EGR1 and IRF-7), while four different transcription factors bind only to the promoter B (HNF1, POU2F1, POU2F2 and PTF1). The predicted transcription factors are mostly involved in regulation of cell differentiation and proliferation. The primer extension experiment performed with primer specific for exon 2-exon 3 junction produced multiple signals of relatively low intensity, indicating the presence of multiple LDLRAD4 transcripts in colon cell lines. The results obtained by in silico analysis may explain promoter B activation in rectal cancer. However, based on the results of primer extension, neither of the LDLRAD4 transcripts is dominant in colon cell lines. Considering that promoter B generates long non-coding RNA that can exert its function even at low expression level, it can serve as potential colorectal cancer biomarker and its potential role in carcinogenesis should be investigated. PB - Croatian Association for Cancer Research, Zagreb, Croatia C3 - “HDIR-6: Targeting Cancer” The 6th Meeting of the Croatian Association for Cancer Research with International Participation – Book of Abstracts T1 - Analysis of Alternative LDLRAD4 Gene Promoters and Transcripts in Colorectal Cancer EP - 35 SP - 35 UR - https://hdl.handle.net/21.15107/rcub_imagine_2084 ER -
@conference{ author = "Velimirov, Luka and Babić, Tamara and Dragičević, Sandra and Nikolić, Aleksandra", year = "2022", abstract = "Gene LDLRAD4 plays a role in cell proliferation, apoptosis, immunosuppression and cancer progression. Transcription of LDLRAD4 is regulated by several alternative promoters, two of which were indicated by in silico analyses to be differentially active in rectal cancer. Promoter A encodes for a truncated protein-coding transcript and is down-regulated in rectal cancer. Promoter B encodes for a non-coding transcript up-regulated in rectal cancer identified as lnc-RNMT-2:5. The aim of this study was to characterize the two alternative promoters in silico in order to explain their differential activity and to investigate the profile of LDLRAD4 transcripts in colon cell lines. Nucleotide sequences used in the analyses were downloaded from the Ensemble genome database (reference GRCh37). Three bioinformatics tools were used for core promoter element prediction: GPMiner, YAPP and CNNPromoter. Four bioinformatics tools were used for transcription factor binding site prediction: PROMO, TFBIND, CiiiDER and Tfsitescan. Only the predictions made by two or more tools were considered. Primer extension followed by fragment analysis was used to characterize LDLRAD4 transcripts present in colon cell lines. The promoter element predictions showed that the promoter A is typical, while promoter B has most typical elements and lacks GC boxes. The transcription binding site predictions indicate that three different transcription factors bind only to the promoter A (NF-kB, EGR1 and IRF-7), while four different transcription factors bind only to the promoter B (HNF1, POU2F1, POU2F2 and PTF1). The predicted transcription factors are mostly involved in regulation of cell differentiation and proliferation. The primer extension experiment performed with primer specific for exon 2-exon 3 junction produced multiple signals of relatively low intensity, indicating the presence of multiple LDLRAD4 transcripts in colon cell lines. The results obtained by in silico analysis may explain promoter B activation in rectal cancer. However, based on the results of primer extension, neither of the LDLRAD4 transcripts is dominant in colon cell lines. Considering that promoter B generates long non-coding RNA that can exert its function even at low expression level, it can serve as potential colorectal cancer biomarker and its potential role in carcinogenesis should be investigated.", publisher = "Croatian Association for Cancer Research, Zagreb, Croatia", journal = "“HDIR-6: Targeting Cancer” The 6th Meeting of the Croatian Association for Cancer Research with International Participation – Book of Abstracts", title = "Analysis of Alternative LDLRAD4 Gene Promoters and Transcripts in Colorectal Cancer", pages = "35-35", url = "https://hdl.handle.net/21.15107/rcub_imagine_2084" }
Velimirov, L., Babić, T., Dragičević, S.,& Nikolić, A.. (2022). Analysis of Alternative LDLRAD4 Gene Promoters and Transcripts in Colorectal Cancer. in “HDIR-6: Targeting Cancer” The 6th Meeting of the Croatian Association for Cancer Research with International Participation – Book of Abstracts Croatian Association for Cancer Research, Zagreb, Croatia., 35-35. https://hdl.handle.net/21.15107/rcub_imagine_2084
Velimirov L, Babić T, Dragičević S, Nikolić A. Analysis of Alternative LDLRAD4 Gene Promoters and Transcripts in Colorectal Cancer. in “HDIR-6: Targeting Cancer” The 6th Meeting of the Croatian Association for Cancer Research with International Participation – Book of Abstracts. 2022;:35-35. https://hdl.handle.net/21.15107/rcub_imagine_2084 .
Velimirov, Luka, Babić, Tamara, Dragičević, Sandra, Nikolić, Aleksandra, "Analysis of Alternative LDLRAD4 Gene Promoters and Transcripts in Colorectal Cancer" in “HDIR-6: Targeting Cancer” The 6th Meeting of the Croatian Association for Cancer Research with International Participation – Book of Abstracts (2022):35-35, https://hdl.handle.net/21.15107/rcub_imagine_2084 .