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Suppression of miR-143 contributes to overexpression of IL-6, HIF-1? and NF-?B p65 in Cr(VI)-induced human exposure and tumor growth.

ABSTRACT: Hexavalent chromium [Cr(VI)] is a known occupational and environmental contaminant and carcinogen, but new mechanisms of Cr(VI)-induced carcinogenesis remain to be elucidated. In this study, we found that expression of miR-143 is decreased, whereas that of Interleukin 6 (IL-6) is increased in blood samples of Cr(VI)-exposing workers compared with corresponding unexposed workers. In addition, IL-6 was increased in human bronchial epithelial cells (BEAS-Cr) exposed to Cr(VI) compared with unexposed BEAS-2B cells. To further investigate the mechanisms by which Cr(VI) promotes these changes, we assessed the effects of miR-143 on gene expression and found that miR-143 suppressed expression of IL-6, HIF-1? and NF-?B p65, and that inhibiting miR-143 promoted expression of IL-6, HIF-1? and NF-?B p65. Interestingly, IL-6 regulated expression of HIF-1?, and HIF-1? transcriptionally regulated expression of IL-6. Experiments in animals showed that miR-143 inhibited tumor growth and angiogenesis by regulating IL-6/HIF-1? and downstream signaling pathways in vivo. These outcomes support the hypothesis that the miR-143/IL-6/HIF-1? pathway functions to regulate Cr(VI)-induced carcinogenesis.

SUBMITTER: Wang L

PROVIDER: S-EPMC6897354 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Suppression of miR-143 contributes to overexpression of IL-6, HIF-1α and NF-κB p65 in Cr(VI)-induced human exposure and tumor growth.

Wang Lin L Qiu Jian-Ge JG He Jun J Liu Wen-Jing WJ Ge Xin X Zhou Feng-Mei FM Huang Ying-Xue YX Jiang Bing-Hua BH Liu Ling-Zhi LZ

Toxicology and applied pharmacology 20190529

Hexavalent chromium [Cr(VI)] is a known occupational and environmental contaminant and carcinogen, but new mechanisms of Cr(VI)-induced carcinogenesis remain to be elucidated. In this study, we found that expression of miR-143 is decreased, whereas that of Interleukin 6 (IL-6) is increased in blood samples of Cr(VI)-exposing workers compared with corresponding unexposed workers. In addition, IL-6 was increased in human bronchial epithelial cells (BEAS-Cr) exposed to Cr(VI) compared with unexpose ...[more]

PMID: 31152816

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Dataset Information

Suppression of miR-143 contributes to overexpression of IL-6, HIF-1? and NF-?B p65 in Cr(VI)-induced human exposure and tumor growth.

Publications

Suppression of miR-143 contributes to overexpression of IL-6, HIF-1α and NF-κB p65 in Cr(VI)-induced human exposure and tumor growth.

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