The DNMT1miR-34aFOXM1 Axis Contributes to Stemness of Liver Cancer Cells
المؤلفون المشاركون
Cao, Xiaocheng
Liu, Lihua
Cao, Xiaozheng
Cui, Yinghong
Zou, Chang
Chen, A.
Qiu, Yebei
Quan, Meifang
Ren, Kaiqun
Chen, Xiangding
Cao, Jianguo
المصدر
العدد
المجلد 2020، العدد 2020 (31 ديسمبر/كانون الأول 2020)، ص ص. 1-15، 15ص.
الناشر
Hindawi Publishing Corporation
تاريخ النشر
2020-03-23
دولة النشر
مصر
عدد الصفحات
15
التخصصات الرئيسية
الملخص EN
Background.
Whether DNA methyltransferase 1 (DNMT1)/miR-34a/FoxM1 signaling promotes the stemness of liver cancer stem cells (LCSCs) remains unclear.
This study aimed to assess whether methylation-based silencing of miR-34a by DNMT1 contributes to stemness features via FoxM1 upregulation in LCSCs.
Methods.
The CD133+ subgroup of MHCC97H cells sorted by MACS was used as LCSCs.
DNMT1, BMI1, SOX2, and OCT4 mRNA levels, and miR-34a amounts were determined by qRT-PCR.
DNMT1, CD44, and FoxM1 proteins were analyzed by immunoblot.
Sphere and colony formation abilities were detected by respective assays.
CD133+ cell percentages were assessed by flow cytometry.
In vivo oncogenicity was evaluated using a tumor xenograft model in mice.
The effects of DNMT1/miR-34a signaling on the stemness of LCSCs were examined by knockdown or overexpression of DNMT1 and/or transfection of miR-34a mimic or inhibitor using lentivirus-delivery systems.
FoxM1 association with miR-34a was detected by a reporter assay.
Results.
We here showed that LCSCs exhibited elevated DNMT1 activity and expression, lower miR-34a expression with higher promoter methylation, and stronger stemness, compared with the parental liver cancer cells.
DNMT1 knockdown repressed DNMT1, increased miR-34a amounts by promoter demethylation, and reduced stemness in LCSCs, whereas DNMT1 overexpression had the opposite effects in liver cancer cells.
Transfection with miR-34a mimic repressed the stemness of LCSCs, while miR-34a inhibitor significantly downregulated miR-34a and enhanced stemness, without affecting DNMT1 in liver cancer cells.
MiR-34a mimic rescued the effects of DNMT1 overexpression on the stemness of LCSCs, without affecting DNMT1 expression.
Finally, FOXM1 was identified as a direct target by miR-34a in LCSCs.
Conclusions.
We revealed that aberrant activation of DNMT1 causes miR-34a promoter methylation and suppression, leading to FoxM1 upregulation by disinhibition and promotion of LCSC stemness.
These findings suggest that blockage of DNMT1/miR-34a-mediated FOXM1 upregulation might suppress liver cancer by targeting LCSCs.
نمط استشهاد جمعية علماء النفس الأمريكية (APA)
Cao, Xiaocheng& Liu, Lihua& Cao, Xiaozheng& Cui, Yinghong& Zou, Chang& Chen, A.…[et al.]. 2020. The DNMT1miR-34aFOXM1 Axis Contributes to Stemness of Liver Cancer Cells. Journal of Oncology،Vol. 2020, no. 2020, pp.1-15.
https://search.emarefa.net/detail/BIM-1189164
نمط استشهاد الجمعية الأمريكية للغات الحديثة (MLA)
Cao, Xiaocheng…[et al.]. The DNMT1miR-34aFOXM1 Axis Contributes to Stemness of Liver Cancer Cells. Journal of Oncology No. 2020 (2020), pp.1-15.
https://search.emarefa.net/detail/BIM-1189164
نمط استشهاد الجمعية الطبية الأمريكية (AMA)
Cao, Xiaocheng& Liu, Lihua& Cao, Xiaozheng& Cui, Yinghong& Zou, Chang& Chen, A.…[et al.]. The DNMT1miR-34aFOXM1 Axis Contributes to Stemness of Liver Cancer Cells. Journal of Oncology. 2020. Vol. 2020, no. 2020, pp.1-15.
https://search.emarefa.net/detail/BIM-1189164
نوع البيانات
مقالات
لغة النص
الإنجليزية
الملاحظات
Includes bibliographical references
رقم السجل
BIM-1189164
قاعدة معامل التأثير والاستشهادات المرجعية العربي "ارسيف Arcif"
أضخم قاعدة بيانات عربية للاستشهادات المرجعية للمجلات العلمية المحكمة الصادرة في العالم العربي
تقوم هذه الخدمة بالتحقق من التشابه أو الانتحال في الأبحاث والمقالات العلمية والأطروحات الجامعية والكتب والأبحاث باللغة العربية، وتحديد درجة التشابه أو أصالة الأعمال البحثية وحماية ملكيتها الفكرية. تعرف اكثر