Cancer Reports
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2022
·Vol. 6
·期 2
·e1688
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IF 0
Ying Liang,Yan Liu,Pin Zhang,Mengxin Zhang,Bang Du,Weyland Cheng,Zhidan Yu,Lifeng Li,Huanmin Wang,Guangjun Hou,Xianwei Zhang,Wancun Zhang
The postoperative recurrence of neuroblastoma (NB) patients is an essential reason for the high mortality of NB due to the lack of early, non-invasive, and dynamic strategies for monitoring NB recurrence. Therefore, whether the plasma circulating cell-free MYCN gene as an indicator for monitoring of NB recurrence was systematically evaluated. The MYCN copy number and NAGK (reference gene) copy number (M/N) ratio in plasma and corresponding tumor tissues of NB patients was detected using an economical, sensitive, and specific single-tube dual RT-PCR approach developed in this study. The plasma M/N ratio of the MYCN gene amplification (MNA) group ( N = 25, median M/N ratio = 4.90) was significantly higher than that of the non-MNA group ( N = 71, median M/N ratio = 1.22), p < .001. The M/N ratio in NB plasma ( N = 60) was positively correlated with the M/N ratio in NB tumor tissue ( N = 60), with a correlation coefficient of 0.9496. In particular, the results of dynamic monitoring of postoperative plasma M/N ratio of NB patients showed that an abnormal increase in M/N ratio could be detected 1–2 months before recurrence in NB patients. In summary, the single-tube double RT-PCR approach can be used to quantitatively detect MYCN copy number. The copy number of MYCN in the tissue and plasma of NB patients is consistent with each other. More importantly, the circulating cell-free MYCN gene of NB patients can be used as a monitoring indicator for early, non-invasive, and dynamic monitoring of NB recurrence.
研究领域:
肿瘤学
·
分子生物学
·
遗传学
✓ 已验证
DOI
PubMed
ANALYTICAL BIOCHEMISTRY
·
2022
·
IF 3.191
Ying Liang,Qionglin Wang,Xianwei Zhang,Mengxin Zhang,Bang Du,Weyland Cheng,Huanmin Wang,Lifeng Li,Guangjun Hou,Wancun Zhang
A dual isothermal amplification assay with dual fluorescence signal detection strategy, named dual isothermal amplification all-in-one approach, was developed for rapid, one-step, highly sensitive quantification of plasma circulating MYCN copy number of neuroblastoma (NB). The developed strategy consisted of rolling circle amplification (RCA) and loop-mediated isothermal amplification (LAMP) on a real-time PCR system using highly specific probe, molecular beacon (MB), as detection probe. The developed strategy possessing a broad linear dynamic range of 10 aM to 1 pM for both target gene ( MYCN ) and reference gene ( NAGK ) . The ratio of the MYCN copy number to NAGK copy number (M/N ratio) was detected by the developed approach in cell lines, NB tumor tissues, hepatoblastoma tumor tissues and Wilms’ tumor tissues, to which the M/N ratios were consistent with previous reports. In particular, the M/N ratio in NB clinical tissue specimens and NB plasma specimens detected with the developed approach were in keeping with the standard RT-PCR approach. More importantly, the M/N ratio in NB tissue samples and corresponding plasma samples of NB patients were consistent with each other with a correlation coefficient of 0.9690, indicating that plasma circulating MYCN is a promising indicator for the risk classification of NB.
研究领域:
肿瘤学
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分子生物学
·
临床诊断
✓ 已验证
DOI
PubMed
高影响因子
MOLECULAR CELL
·
2024
·
IF 14.5
Huihui An,Yifan Hong,Yeek Teck Goh,Casslynn W.Q. Koh,Shahzina Kanwal,Yi Zhang,Zhaoqi Lu,Phoebe M.L. Yap,Suat Peng Neo,Chun-Ming Wong,Alice S.T. Wong,Yang Yu,Jessica Sook Yuin Ho,Jayantha Gunaratne,Wee Siong Sho Goh
N 6 ,2′-O-dimethyladenosine (m 6 Am) is an abundant mRNA modification that impacts multiple diseases, but its function remains controversial because the m 6 Am reader is unknown. Using quantitative proteomics, we identified transcriptional terminator premature cleavage factor II (PCF11) as a m 6 Am-specific reader in human cells. Direct quantification of mature versus nascent RNAs reveals that m 6 Am does not regulate mRNA stability but promotes nascent transcription. Mechanistically, m 6 Am functions by sequestering PCF11 away from proximal RNA polymerase II (RNA Pol II). This suppresses PCF11 from dissociating RNA Pol II near transcription start sites, thereby promoting full-length transcription of m 6 Am-modified RNAs. m 6 Am’s unique relationship with PCF11 means m 6 Am function is enhanced when PCF11 is reduced, which occurs during all- trans -retinoic-acid (ATRA)-induced neuroblastoma-differentiation therapy. Here, m 6 Am promotes expression of ATF3, which represses neuroblastoma biomarker MYCN. Depleting m 6 Am suppresses MYCN repression in ATRA-treated neuroblastoma and maintains their tumor-stem-like properties. Collectively, we characterize m 6 Am as an anti-terminator RNA modification that suppresses premature termination and modulates neuroblastoma’s therapeutic response.
研究领域:
分子生物学
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癌症生物学
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转录组学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Oncology
·
2021
·
IF 6.244
Hu Zengchun,Cheng Chuandong,Wang Yue,Chen Tianrui,Tu Junhong,Niu Chaoshi,Xing Rong,Wang Yang,Xu Yinghui
Neuroblastoma is the most common extracranial neuroendocrine tumor in childhood. Although many studies have tried to find effective treatments, there are still numerous limitations in current clinical targeted therapy. So, it is important to find new therapeutic targets and strategies from a new perspective. Our previous study reported that the androgen receptor (AR) promotes the growth of neuroblastoma in vitro and in vivo. Based on documentary investigation, we postulated that the AR–SCAP–SREBPs-CYP17/HMGCR axis may regulate cholesterol and androgens synthesis and form a positive enhancement loop promoting NB progression. Clinical samples and Oncomine database analysis proved the activation of AR–SCAP–SREBPs-CYP17/HMGCR axis in neuroblastoma. The combination of inhibitors of HMGCR (statins) and CYP17A1 (abiraterone acetate) showed synergistic effect that significantly inhibited the proliferation and migration with decreased expression of related genes detected in vitro and in vivo suggesting the dual-targeted therapy had the potential to inhibit the progression of neuroblastoma in spite of its MYCN status. This study provides new ideas for clinical treatment of neuroblastoma with efficacy and reduced toxicity.
研究领域:
肿瘤学
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药理学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nature Communications
·
2024
·Vol. 15
·期 1
·1-17
·
IF 14.7
Wu Min,Wang Tingting,Ji Nan,Lu Ting,Yuan Ran,Wu Lingxiang,Zhang Junxia,Li Mengyuan,Cao Penghui,Zhao Jiarui,Li Guanzhang,Li Jianyu,Li Yu,Tang Yujie,Gao Zhengliang,Wang Xiuxing,Cheng Wen,Ge Ming,Cui Gang,Li Rui,Wu Anhua,You Yongping,Zhang Wei,Wang Qianghu,Chen Jian
Glioblastoma (GBM) is the most common brain tumor and remains incurable. Primary GBM cultures are widely used tools for drug screening, but there is a lack of genomic and pharmacological characterization for these primary GBM cultures. Here, we collect 50 patient-derived glioma cell (PDGC) lines and characterize them by whole genome sequencing, RNA sequencing, and drug response screening. We identify three molecular subtypes among PDGCs: mesenchymal (MES), proneural (PN), and oxidative phosphorylation (OXPHOS). Drug response profiling reveals that PN subtype PDGCs are sensitive to tyrosine kinase inhibitors, whereas OXPHOS subtype PDGCs are sensitive to histone deacetylase inhibitors, oxidative phosphorylation inhibitors, and HMG-CoA reductase inhibitors. PN and OXPHOS subtype PDGCs stably form tumors in vivo upon intracranial transplantation into immunodeficient mice, whereas most MES subtype PDGCs fail to form tumors in vivo. In addition, PDGCs cultured by serum-free medium, especially long-passage PDGCs, carry MYC/MYCN amplification, which is rare in GBM patients. Our study provides a valuable resource for understanding primary glioma cell cultures and clinical translation and highlights the problems of serum-free PDGC culture systems that cannot be ignored.
研究领域:
肿瘤学
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基因组学
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药理学
·
神经科学
✓ 已验证
DOI
PubMed
高影响因子
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