# Chromium in carcinogenesis and angiogenesis

> **NIH NIH R01** · THOMAS JEFFERSON UNIVERSITY · 2020 · $307,764

## Abstract

Hexavalent chromium [Cr(VI)] long-term exposure is associated with human lung cancer. Although there is
emerging interest in the mechanism underlying Cr(VI)-induced carcinogenesis, the mechanism and role of
Cr(VI) in inducing carcinogenesis still remains to be elucidated. In preliminary studies, we used human
peripheral blood mononuclear cells (PBMC cells) from Cr(VI) exposed and control subjects to perform whole
genome expression array analysis, and found that IL-8 and CXCL5 are the two most up-regulated genes
detected in the exposure group compared with non-exposure subjects. We validated our findings by RT-qPCR
and ELISA assay. Additionally, we found that miR-199a suppression and β-catenin upregulation are important
for IL-8 and CXCL5 induction. Forced expression of miR-199a and knockdown of IL-8 or CXCL5 inhibited both
cell transformation and angiogenesis. These findings are consistent with our results obtained from Cr(VI)-
transformed cells and from in vitro studies. Furthermore, we found that β-catenin directly activated IL-8
expression at transcriptional level, while miR-199a directly targets hypoxia-inducible factor 1
(HIF-1) for inhibiting HIF-1 expression. We hypothesize that miR-199a suppression and β-catenin
upregulation are important in Cr(VI)-induced tumorigenesis and angiogenesis through induction of IL-
8 and CXCL5 expression. Tumor cell growth and angiogenesis are the important characteristics of
carcinogenesis, transformation from normal cells to cancer cells. In order to test this hypothesis, we will
perform three specific aims: Aim 1) To determine role of miR-199a suppression and β-catenin upregulation in
Cr(VI)-induced cell transformation, and identify the mechanism of IL-8 and CXCL5 elevation. Aim 2) To
determine roles of miR-199a, β-catenin, IL-8, and CXCL5 in Cr(VI) transformed cell-induced tumor growth. Aim
3) To determine whether Cr-T cells induce tumor angiogenesis through IL-8 receptors using chimeric tumor
model and determine expression levels of IL-8, CXCL5, β-catenin, and miR-199a in peripheral blood
mononuclear cells (PBMCs) and plasma, and the possible correlations with Cr(VI) internal exposure doses in
workers with occupational Cr(VI) exposure. We will use a combination of molecular approaches, a n animal
model, and blood and tissue samples from human subjects to define roles and mechanisms of miR-199a, β-
catenin, IL-8, and CXCL5 in Cr(VI)-induced cell transformation, tumor growth, and angiogenesis. These
studies will not only help us understand the underlying mechanisms of Cr(VI) in inducing carcinogenesis, but
also identify potential new biomarkers for early detection of Cr(VI) exposure of workers in electroplating
factories in the future.

## Key facts

- **NIH application ID:** 10328704
- **Project number:** 7R01ES027901-04
- **Recipient organization:** THOMAS JEFFERSON UNIVERSITY
- **Principal Investigator:** BingHua Jiang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $307,764
- **Award type:** 7
- **Project period:** 2018-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10328704

## Citation

> US National Institutes of Health, RePORTER application 10328704, Chromium in carcinogenesis and angiogenesis (7R01ES027901-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10328704. Licensed CC0.

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