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. 2018 Aug 16;13(8):e0202579.
doi: 10.1371/journal.pone.0202579. eCollection 2018.

miRNA expression profiles of premalignant and malignant arsenic-induced skin lesions

Laila Al-Eryani  1 , Samantha F Jenkins  1 , Vanessa A States  2 , Jianmin Pan  3 , Janine C Malone  4 , Shesh N Rai  3   5 , Susan Galandiuk  2 , Ashok K Giri  6 , J Christopher States  1
Affiliations

miRNA expression profiles of premalignant and malignant arsenic-induced skin lesions

Laila Al-Eryani et al. PLoS One. .

Abstract

Arsenic, a naturally occurring element, contaminates the drinking water of over 200 million people globally. Chronic arsenic exposure causes multiple cancers including those originating from skin, lung and bladder, and is associated with liver, kidney, and prostate cancers. Skin is the primary target organ for arsenic toxicity; chronic toxicity initially manifests as non-malignant hyperkeratoses (HK) and subsequently advances to malignant lesions, including squamous cell carcinoma (SCC) and basal cell carcinoma (BCC). In this study, we evaluate the miRNA expression profiles of premalignant (3 HK) and malignant (3 BCC and 3 SCC) skin lesions from individuals chronically exposed to high levels of arsenic (59-172 ppb) in their drinking water in West Bengal, India. The lesions were histologically complex requiring histopathologic identification of keratinocytes to be isolated for RNA analyses. Keratinocytes were harvested using Laser Capture Microdissection and miRNA expression profiles were determined using TaqMan® Array Human MiRNA A Card v2.0. Thirty-five miRNAs were differentially expressed among the three lesion types analyzed. Two miRNAs (miR-425-5p and miR-433) were induced in both BCC and SCC relative to HK indicating their association with malignancy. Two other miRNAs (miR-184 and miR-576-3p) were induced in SCC relative to both BCC and HK suggesting selective induction in tumors capable of metastasis. Six miRNAs (miR-29c, miR-381, miR-452, miR-487b, miR-494 and miR-590-5p) were selectively suppressed in BCC relative to both SCC and HK. In conclusion, the differential miRNA expression was both phenotype- and stage-related. These miRNAs are potential biomarkers and may serve as therapy targets for arsenic-induced internal tumors.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Arsenic-induced skin cancer progression.
Progression from the premalignant hyperkeratosis lesion (HK) to either of the malignant lesions, basal cell carcinoma (BCC) directly or squamous cell carcinoma (SCC) through Bowen’s disease (BD, SCC in situ). Shown are photographs of lesions in situ prior to excision with a histological section of the formalin fixed and paraffin embedded sample stained with hematoxylin and eosin on the right.
Fig 2
Fig 2. Arsenic induced premalignant and malignant skin lesions.
Histological sections of arsenic-induced basal cell carcinoma, squamous cell carcinoma and hyperkeratosis. A. Basal cell carcinoma, arrows point to inflammatory foci. B. Squamous cell carcinoma, arrows point to inflammatory foci. C. Hyperkeratosis with dysplasia, arrows point to areas of dysplasia projecting from the hyperkeratotic region. D. Hyperkeratosis without dysplasia.
Fig 3
Fig 3. Differentially expressed miRNA in arsenic-induced skin lesions.
Differential expression comparisons are diagrammed. Differentially expressed miRNAs in: A. malignant lesions, both BCC and SCC relative to HK; B. Specific to SCC vs HK or BCC; C. Specific to BCC vs SCC or HK. Direction of expression changes indicated by arrows. Additional differentially expressed miRNAs are listed in S1 Table.
See this image and copyright information in PMC

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