تغريد جمال الدين عبد الرحمن
أستاذ
Epigenetic alterations of miR‑155 and global DNA methylation as potential mediators of ochratoxin A cytotoxicity and carcinogenicity in human lung fibroblasts
Environmental Science and Pollution Research • 2023
معلومات البحث
المؤلفون
Taghrid G. Kharboush1 · Inas A. Ahmed2,3 · Amina A. Farag4 · Tayseir Kharboush5 · Alaa El‑Din H. Sayed6,7 ·
Amal M. Abdel‑Kareim8 · Mohammed Al mohaini9,10 · Hend Attia11 · Refaat A. Eid12 · Mohamed Samir A. Zaki13 ·
Al‑Shaimaa M. Al‑Tabbakh
الكلمات المفتاحية
Ochratoxin A 1; Epigenetics 2; miRNA-155 3 · DNA methylation 4 · Cytotoxicity 5 lung cells
المجلة العلمية
Environmental Science and Pollution Research
الناشر
springer
المجلد
31
العدد
Not Available
الصفحات
5473–5483
publication.type
International
رابط البحث
Not Available
المواد المرفقة
Not Available
الملخص
Ochratoxin A (OTA) is a well-known mycotoxin that adversely affects different human cells. Inhalational exposure to OTA
and subsequent pulmonary diseases have been previously reported, yet its potential carcinogenicity and underlying molecular
mechanisms have not been fully elucidated. This study aimed to evaluate the OTA-induced cytotoxicity and the epigenetic
changes underlying its potential carcinogenicity in fetal lung fibroblast (WI-38) cells. OTA cytotoxicity was assessed by
MTT assay; RT-qPCR was used to determine the expression of BAX, BCL-2, TP53, and miR-155, while ELISA was used for
measuring 5-methyl cytosine percentage to assess global DNA methylation in OTA-treated versus control cells. WI-38 cells
demonstrated sensitivity to OTA with IC50 at 22.38 μM. Though BAX and Bcl-2 were downregulated, with low BAX/BCL-2
ratio, and TP53 was upregulated, their fold changes showed decline trend with increasing OTA concentration. A significant
dose-dependent miR-155 upregulation was observed, with dynamic time-related decline. Using subtoxic OTA concentra-
tions, a significant global DNA hypermethylation with significant dose-dependent and dynamic alterations was identified.
Global DNA hypermethylation and miR-155 upregulation are epigenetic mechanisms that mediate OTA toxicity on WI-38
cells. BAX downregulation, reduced BAX/BCL-2 ratio together with miR-155 upregulation indicated either the inhibition
of TP53-dependent apoptosis or a tissue specific response to OTA exposure. The aforementioned OTA-induced variations
present a new molecular evidence of OTA cytotoxicity and possible carcinogenicity in lung fibroblast cells.
and subsequent pulmonary diseases have been previously reported, yet its potential carcinogenicity and underlying molecular
mechanisms have not been fully elucidated. This study aimed to evaluate the OTA-induced cytotoxicity and the epigenetic
changes underlying its potential carcinogenicity in fetal lung fibroblast (WI-38) cells. OTA cytotoxicity was assessed by
MTT assay; RT-qPCR was used to determine the expression of BAX, BCL-2, TP53, and miR-155, while ELISA was used for
measuring 5-methyl cytosine percentage to assess global DNA methylation in OTA-treated versus control cells. WI-38 cells
demonstrated sensitivity to OTA with IC50 at 22.38 μM. Though BAX and Bcl-2 were downregulated, with low BAX/BCL-2
ratio, and TP53 was upregulated, their fold changes showed decline trend with increasing OTA concentration. A significant
dose-dependent miR-155 upregulation was observed, with dynamic time-related decline. Using subtoxic OTA concentra-
tions, a significant global DNA hypermethylation with significant dose-dependent and dynamic alterations was identified.
Global DNA hypermethylation and miR-155 upregulation are epigenetic mechanisms that mediate OTA toxicity on WI-38
cells. BAX downregulation, reduced BAX/BCL-2 ratio together with miR-155 upregulation indicated either the inhibition
of TP53-dependent apoptosis or a tissue specific response to OTA exposure. The aforementioned OTA-induced variations
present a new molecular evidence of OTA cytotoxicity and possible carcinogenicity in lung fibroblast cells.