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Toxicology. 2017 Mar 1;378:10-16. doi: 10.1016/j.tox.2017.01.006. Epub 2017 Jan 6.

Increased microRNA 21 expression contributes to arsenic induced skin lesions, skin cancers and respiratory distress in chronically exposed individuals.

Author information

1
Cell Biology and Physiology Division, CSIR-Indian Institute of Chemical Biology, Kolkata 700032, India. Electronic address: 2006.nilanjana@gmail.com.
2
Health Point Multispecialty Hospital, Kolkata 700025, India; Ramakrishna Sarada Mission Matri Bhavan, Kolkata 700026, India. Electronic address: drapurba59@gmail.com.
3
Molecular Genetics Division, CSIR-Indian Institute of Chemical Biology, Kolkata 700032, India. Electronic address: suman29oct@gmail.com.
4
Department of Dermatology, West Bank Hospital, Howrah 711109, India. Electronic address: jayantadas62@gmail.com.
5
Department of Environmental Studies, School of Environmental Studies, Jadavpur University, Kolkata 700032, India. Electronic address: troychowdhury_envstu@school.jdvu.ac.in.
6
Cell Biology and Physiology Division, CSIR-Indian Institute of Chemical Biology, Kolkata 700032, India. Electronic address: arun@iicb.res.in.
7
Molecular Genetics Division, CSIR-Indian Institute of Chemical Biology, Kolkata 700032, India. Electronic address: akgiri15@yahoo.com.

Abstract

More than 26 million people in West Bengal, India, are exposed to arsenic through drinking water, leading to several deleterious endpoints including precancerous and cancerous skin lesions and other non-dermatological health effects. Here, our aim was to identify whether miR21 is associated with such dermatological and non-dermatological health outcomes in chronically exposed humans. A total of 123 subjects from West Bengal were recruited for this study (45 exposed individuals with skin lesions, 38 exposed individuals without skin lesions and 40 unexposed individuals). The miR21 expression patterns in the lymphocytes were studied by quantitative realtime PCR and the effects on downstream targets were validated by Western blotting. Associations between the miR21 expression patterns and non-dermatological health effects were determined from epidemiological survey data. In vitro studies were done with low dose (0.05ppm) of chronic arsenic exposure to HaCaT cells for 15 passages. Interestingly, within the exposed group, the skin lesion individuals showed almost 4.5 fold up-regulation of miR21 compared to the no skin lesion group. The expression of the downstream targets of miR21 (PTEN and PDCD4) varied inversely, while the expression of pAKT and PI3K varied proportionately with its expression levels. Results of in vitro studies showed similar trends. Again miR21 was 2.03 fold up-regulated in the exposed individuals with respiratory diseases compared to the individuals without the same. This study for the first time shows that miR21 plays an important role in contributing to arsenic induced dermatological and non-dermatological health outcomes in an exposed population.

KEYWORDS:

Arsenic; Human; Micro RNA 21; Respiratory problems; Skin cancer; Susceptibility

PMID:
28069514
DOI:
10.1016/j.tox.2017.01.006
[Indexed for MEDLINE]

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