Long Noncoding RNA ABHD11-AS1 Interacts with SART3 and Regulates CD44 RNA Alternative Splicing to Promote Lung Carcinogenesis

Details

• Personal Author:
  Chen J ; Liu Z ; Sweef O ; Wang P-S ; Wang Z ; Xie J ; Yang C ; Zeidler-Erdely PC ; Zhu H
• Description:
  Hexavalent chromium [Cr(VI)] is a common environmental pollutant and chronic exposure to Cr(VI) causes lung cancer in humans, however, the mechanism of Cr(VI) carcinogenesis has not been well understood. Lung cancer is the leading cause of cancer-related death, although the mechanisms of how lung cancer develops and progresses have been poorly understood. While long non-coding RNAs (lncRNAs) are found abnormally expressed in cancer, how dysregulated lncRNAs contribute to carcinogenesis remains largely unknown. The goal of this study is to investigate the mechanism of Cr(VI)-induced lung carcinogenesis focusing on the role of the lncRNA ABHD11 antisense RNA 1 (tail to tail) (ABHD11-AS1). It was found that the lncRNA ABHD11-AS1 expression levels are up-regulated in chronic Cr(VI) exposure-transformed human bronchial epithelial cells, chronically Cr(VI)-exposed mouse lung tissues, and human lung cancer cells as well. Bioinformatics analysis revealed that ABHD11-AS1 levels are up-regulated in lung adenocarcinomas (LUADs) tissues and associated with worse overall survival of LUAD patients but not in lung squamous cell carcinomas. It was further determined that up-regulation of ABHD11-AS1 expression plays an important role in chronic Cr(VI) exposure-induced cell malignant transformation and tumorigenesis, and the stemness of human lung cancer cells. Mechanistically, it was found that ABHD11-AS1 directly binds SART3 (spliceosome associated factor 3, U4/U6 recycling protein). The interaction of ABHD11-AS1 with SART3 promotes USP15 (ubiquitin specific peptidase 15) nuclear localization. Nuclear localized USP15 interacts with pre-mRNA processing factor 19 (PRPF19) to increase CD44 RNA alternative splicing activating β-catenin and enhancing cancer stemness. Together, these findings indicate that lncRNA ABHD11-AS1 interacts with SART3 and regulates CD44 RNA alternative splicing to promote cell malignant transformation and lung carcinogenesis. [Description provided by NIOSH]
• Subjects:
  Carcinogens Chromium Environmental Exposure Lung Lung Diseases Neoplasms Occupational Exposure Occupational Health Respiratory System Respiratory Tract Diseases Safety

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• Keywords:
  ABHD11-AS1 Author Keywords: Hexavalent Chromium Carcinogenesis CD44 Chronic Exposure Environmental Exposure Genetic Factors Hexavalent Chromium Long Non-coding RNA Lung Cancer SART3 USP15

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• ISSN:
  0160-4120
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  Kentucky ; New York ; Ohio ; OSHA Region 2 ; OSHA Region 3 ; OSHA Region 4 ; OSHA Region 5 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  185
• NIOSHTIC Number:
  nn:20069256
• Citation:
  Environ Int 2024 Mar; 185:108494
• Contact Point Address:
  Zhishan Wang, Stony Brook Cancer Center, Department of Pathology, Stony Brook University, Stony Brook, NY, USA
• Email:
  zhishan.wang@stonybrook.edu
• CAS Registry Number:
  Chromium(6+) (CAS RN 18540-29-9)
• Federal Fiscal Year:
  2024
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  True
• Source Full Name:
  Environmental International
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:bd9de775cc940e3593a693aa0f8d48a0dd7823212a5902a4f741cc57ff9d1180d5bfb8053976877da6a89a78524914f2a7c68322766816887c27888fb89d734c
• Download URL:
  https://stacks.cdc.gov/view/cdc/207763/cdc_207763_DS1.pdf
• File Type:
  [PDF - 11.62 MB ]