PARP-1 inhibits DNMT1-mediated promoter methylation and promotes linc01132 expression in benzene-exposed workers and hydroquinone-induced malignant transformed cells

Zhang, Haiqiao; Jiang, Fuman; Ling, Xiaoxuan; Zhong, Bohuan; Han, Yali; Pan, Zhijie; Yuan, Qian; Meng, Jinxue; Zheng, Dongyan; Chen, Xiaobing; Zhong, Qinghua; Liu, Linhua

doi:10.1080/15376516.2023.2220389

“…In Haiqiao Zhang's 2023 research, it is noted that PARP-1 impedes DNA methyltransferase (DNMT)-guided promoter methylation and plays a role in the expression of linc01132 in workers exposed to benzene or HQ-MT cells. Additionally, this process is linked to the onset of leukemia induced by benzene or HQ [64].…”

Section: Discussionmentioning

confidence: 99%

LINC01132 and LINC02542 modulate the PIK3/ACT signaling pathway in colorectal cancer patients through regulation of IGF2: a systems biology-based biomarker discovery

Jalalimanesh,

Azadeh,

Sasan

et al. 2024

Preprint

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Background There is ample evidence to suggest that colorectal cancer has unique originations and genetic changes and immune profiles indicating that colorectal cancer is a diverse disease. Long non-coding RNAs (lncRNAs) perform different duties in controlling gene transcription, post-transcriptional mechanisms, translation, and epigenetic changes. dysregulated expression of lncRNAs is closely associated with a variety of medical conditions. Method A comprehensive bioinformatics analysis was conducted to make an informed prediction about the potential biomarkers. The selection of RNAs for this investigation was based on Microarray data analysis, enrichment analyses (pathway, GO), and direct/indirect interaction. Various statistical methods were used to assess differences in expression in the CRC samples, RNA correlations, and the potential for consideration as prognostic or diagnostic biomarkers (ROC and clinicopathological analysis). Result The bioinformatics analysis revealed that LINC01132 (logFC: 2.361870571, adj. P. Val < 0.05) and LINC02542 (logFC: 2.456774839, adj. P. Val < 0.05) are significantly up-regulated in CRC and have the potential to be diagnostic biomarkers for the disease, as indicated by their high area under the curve (AUC) values (LINC01132, AUC:0/9475, P. Value <0.0001 and LINC02542, AUC: 0/9075, P. Value <0.0001). Additionally, LINC02542 was found to have a positive correlation with the survival rate of CRC cases (HR: 1.8, log-rank p: 0.02). Both LINC01132 and LINC02542 were found to interact with IGF2(sum of local base-pairing energy of LINC02542: -354.52 kcal/mol, and energy of LINC01132: -69.82 kcal/mol). Conclusion LINC01132 and LINC02542 are novel lncRNAs in CRC, and Let-7e-5p miRNA may modulate the PI3K-AKT signaling pathway in CRC through indirect effects on IGF2.

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“…9 In addition, PARP-1 inhibited DNMT1-mediated promoter methylation and promoted the expression of linc01132 in benzene-exposed workers and in HQ-induced malignant transformed cells. 10 We found that HQ can cause epigenetic modifications such as alterations in DNA methylation and the expression of miRNAs, long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs). 4,8,9,11 However, how circRNA is involved in epigenetic changes in HQ-TK6 cells remains to be further studied.…”

Section: Introductionmentioning

confidence: 99%

DNMT1 regulates hypermethylation and silences hsa_circ_401351 in hydroquinone‐induced malignant TK6 cells

Han,

Meng,

Ling

et al. 2023

Environmental Toxicology

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BackgroundBenzene and its metabolite hydroquinone (HQ) are widely used in daily life, and long‐term exposure to benzene or HQ can induce acute myeloid leukemia (AML). Circular RNAs (circRNAs) are mostly produced by reverse splicing of gene exon mRNA precursors. The modulation of circRNA expression is connected to leukemia progression; however, the molecular mechanism is still unknown.Materials and methodsIn this study, the cells were divided into four groups: PBS control group (PBS‐TK6), TK6 malignantly transformed cells induced by 10.0 μmol/L HQ (HQ‐TK6), and HQ‐TK6 cells treated with 5 μmol/L 5‐AzaC (DNA methyltransferase inhibitor) for 24 h (HQ + 5‐AzaC). HQ‐TK6 cells were treated with 200 nmol/L TSA (histone deacetylation inhibitor) for 24 h (HQ + TSA). qRT–PCR was used to identify the differential hsa_circ_401351 expression between the four groups. We further determined the hsa_circ_401351 promoter methylation level with methylation‐specific PCR. DNMT1 and DNMT3b were knocked down by CRISPR/Cas9 to elucidate the specific molecular mechanism of hsa_circ_401351 in HQ‐TK6 cells. CCK‐8 and flow cytometry detected cell proliferation and apoptosis, respectively, after hsa_circ_401351 was overexpressed in HQ‐TK6 cells.ResultsCompared with the PBS‐TK6 group, the expression of hsa_circ_401351 was found to be lower in the HQ‐TK6 group. Nevertheless, treatment with 5‐AzaC or TSA increased hsa_circ_401351 expression, with the upregulation being more pronounced in the TSA group. The expression of hsa_circ_401351 in the DNMT1 knockdown group was dramatically increased by 50% compared to that in the control group, and the DNA methylation level of the hsa_circ_401351 promoter region was decreased. When hsa_circ_401351 was overexpressed, HQ‐TK6 cell proliferation was significantly slowed after 48 h compared with the control group. Flow cytometry showed that cells were mainly arrested in G1 phase, and apoptosis was significantly enhanced. Similarly, qRT–PCR and Western blot data showed significant reductions in Caspase‐3 mRNA and protein production, and Bcl‐2 mRNA levels were also elevated.ConclusionsOverall, our research showed that elevated DNMT1 expression in HQ‐TK6 cells increased methylation levels and decreased expression of the hsa_circ_401351 promoter region, limiting its ability to suppress HQ‐TK6 cell growth and enhance apoptosis.

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LINC01132 and LINC02542 modulate the PIK3/ACT signaling pathway in breast cancer patients through regulation of IGF2: a systems biology-based biomarker discovery

Jalalimanesh,

Azadeh,

Sasan

et al. 2024

Preprint

0

View full text Add to dashboard Cite

Background There is ample evidence to suggest that colorectal cancer has unique originations and genetic changes and immune profiles indicating that colorectal cancer is a diverse disease. Long non-coding RNAs (lncRNAs) perform different duties in controlling gene transcription, post-transcriptional mechanisms, translation, and epigenetic changes. dysregulated expression of lncRNAs is closely associated with a variety of medical conditions. Method A comprehensive bioinformatics analysis was conducted to make an informed prediction about the potential biomarkers. The selection of RNAs for this investigation was based on Microarray data analysis, enrichment analyses (pathway, GO), and direct/indirect interaction. Various statistical methods were used to assess differences in expression in the CRC samples, RNA correlations, and the potential for consideration as prognostic or diagnostic biomarkers (ROC and clinicopathological analysis). Result The bioinformatics analysis revealed that LINC01132 (logFC: 2.361870571, adj. P. Val < 0.05) and LINC02542 (logFC: 2.456774839, adj. P. Val < 0.05) are significantly up-regulated in CRC and have the potential to be diagnostic biomarkers for the disease, as indicated by their high area under the curve (AUC) values (LINC01132, AUC:0/9475, P. Value <0.0001 and LINC02542, AUC: 0/9075, P. Value <0.0001). Additionally, LINC02542 was found to have a positive correlation with the survival rate of CRC cases (HR: 1.8, log-rank p: 0.02). Both LINC01132 and LINC02542 were found to interact with IGF2(sum of local base-pairing energy of LINC02542: -354.52 kcal/mol, and energy of LINC01132: -69.82 kcal/mol). Conclusion LINC01132 and LINC02542 are novel lncRNAs in CRC, and Let-7e-5p miRNA may modulate the PI3K-AKT signaling pathway in CRC through indirect effects on IGF2.

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PARP-1 inhibits DNMT1-mediated promoter methylation and promotes linc01132 expression in benzene-exposed workers and hydroquinone-induced malignant transformed cells

Cited by 3 publications

References 35 publications

LINC01132 and LINC02542 modulate the PIK3/ACT signaling pathway in colorectal cancer patients through regulation of IGF2: a systems biology-based biomarker discovery

LINC01132 and LINC02542 modulate the PIK3/ACT signaling pathway in colorectal cancer patients through regulation of IGF2: a systems biology-based biomarker discovery

DNMT1 regulates hypermethylation and silences hsa_circ_401351 in hydroquinone‐induced malignant TK6 cells

LINC01132 and LINC02542 modulate the PIK3/ACT signaling pathway in breast cancer patients through regulation of IGF2: a systems biology-based biomarker discovery

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