Arsenic Induces Cytotoxicity in Pulmonary Epithelial Cells by Regulating the MicroRNA‐195‐5p/E2F7 Axis: The Impact of Tannic Acid From Natural Sources

As a result of both natural and anthropogenic causes, arsenic (As), a toxic metalloid element, is constantly encountered in various environmental matrices. Unusual damage and death of pulmonary epithelial cells are strongly connected with exposure to numerous environmental pollutants, which can further lead to the incidence of many lung diseases. In our recent study, we have shown that a higher expression of microRNA‐195‐5p (miRNA‐195‐5p) is associated with arsenic (As 3+ )‐induced pulmonary epithelial cell death. Therefore, this study was conducted to identify the molecular mechanism underlying the miR‐195‐5p‐mediated cell death of As 3+ ‐exposed pulmonary epithelial cells. Further, we also explored the role of polyphenol tannic acid (TA) from natural sources on As 3+ ‐induced cytotoxicity. Results once again confirmed that miR‐195‐5p was markedly upregulated in As 3+ ‐treated (1 μM) human bronchial (BEAS‐2B) and adenocarcinomic alveolar basal (A549) epithelial cell lines, which led to a significant cell death. Moreover, anti‐miR‐195‐5p suppressed As 3+ ‐mediated cytotoxic effects. Computational algorithms identified that E2F transcription factor 7 (E2F7) may be a direct target of miR‐195‐5p. Subsequent studies showed that As 3+ treatment as well as miR‐195‐5p overexpression caused the inhibition of E2F7 at both mRNA and protein levels. Whereas, restoration of E2F7 expression attenuated As 3+ ‐induced cell death in BEAS‐2B cells, indicating that miR‐195‐5p promotes As 3+ ‐mediated cytotoxicity through suppressing E2F7 expression. Results further revealed that TA pre‐treatment protected BEAS‐2B cells from As 3+ ‐induced toxicity by regulating the miR‐195‐5p/E2F7 axis.