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Engineering Artificial Factors to Specifically Manipulate Alternative Splicing in Human Cells
Published on: April 26, 2017
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Long noncoding RNA ABHD11-AS1 interacts with SART3 and regulates CD44 RNA alternative splicing to promote lung
Po-Shun Wang1, Zulong Liu1, Osama Sweef2
1Stony Brook Cancer Center, Stony Brook University, Stony Brook, NY, USA; Division of Cancer Biology, Department of Medicine, MetroHealth Medical Center, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
Environment International
|February 16, 2024
Summary
Hexavalent chromium (Cr(VI)) exposure upregulates the long non-coding RNA ABHD11-AS1, promoting lung cancer development and stemness by altering CD44 RNA splicing. This finding clarifies a key mechanism in Cr(VI)-induced lung carcinogenesis.
Area of Science:
- Environmental Health
- Molecular Biology
- Cancer Research
Background:
- Hexavalent chromium (Cr(VI)) is an environmental pollutant linked to human lung cancer, but its carcinogenic mechanisms are unclear.
- Lung cancer remains a leading cause of cancer death, with poorly understood developmental and progression pathways.
- Long non-coding RNAs (lncRNAs) are implicated in cancer, yet their specific roles in carcinogenesis require further elucidation.
Purpose of the Study:
- To investigate the role of lncRNA ABHD11-AS1 in Cr(VI)-induced lung carcinogenesis.
- To elucidate the molecular mechanisms by which ABHD11-AS1 contributes to malignant transformation and cancer stemness.
Main Methods:
- Analysis of ABHD11-AS1 expression in Cr(VI)-exposed cells, mouse lung tissues, and human lung cancer samples.
- Bioinformatic analysis correlating ABHD11-AS1 levels with patient survival in lung adenocarcinoma (LUAD).
- Investigation of the interaction between ABHD11-AS1, SART3, USP15, PRPF19, and CD44 alternative splicing.
Main Results:
- ABHD11-AS1 expression is significantly upregulated in Cr(VI)-exposed cells, tissues, and human lung cancer cells, particularly LUAD.
- Elevated ABHD11-AS1 correlates with worse overall survival in LUAD patients.
- ABHD11-AS1 directly binds SART3, promoting USP15 nuclear localization, which enhances CD44 alternative splicing, activating β-catenin and cancer stemness.
Conclusions:
- lncRNA ABHD11-AS1 plays a critical role in Cr(VI)-induced lung carcinogenesis and cancer stemness.
- The ABHD11-AS1/SART3/USP15 pathway regulates CD44 alternative splicing, contributing to malignant transformation.
- These findings provide novel insights into the molecular mechanisms of environmental carcinogen-induced lung cancer.
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