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Updated: Aug 4, 2025

Dual CRISPR-Interference Strategy for Targeting Synthetic Lethal Interactions Between Non-Coding RNAs in Cancer Cells
Published on: May 30, 2025
The landscape of cryptic antisense transcription in human cancers reveals an oncogenic noncoding RNA in lung cancer
Zhaozhao Zhao1,2, Yu Chen1, Xiaomeng Cheng1
1State Key Laboratory of Genetic Engineering, National Clinical Research Center for Aging and Medicine, Huashan Hospital, Collaborative Innovation Center of Genetics and Development, Human Phenome Institute, Shanghai Engineering Research Center of Industrial Microorganisms, School of Life Sciences, Fudan University, Shanghai 200438, China.
Abstract:
Cryptic transcription initiation has been previously linked to activation of oncogenic transcripts. However, the prevalence and impact of cryptic antisense transcription from the opposite strand of protein-coding genes were mostly unknown in cancer. Applying a robust computational pipeline to publicly available transcriptome and epigenome datasets, we identified hundreds of previously unannotated cryptic antisense polyadenylated transcripts (CAPTs) that were enriched in tumor samples. We showed that the activation of cryptic antisense transcription was associated with increased chromatin accessibility and active histone marks. Accordingly, we found that many of the antisense transcripts were inducible by treatment of epigenetic drugs. Moreover, CRISPR-mediated epigenetic editing assays revealed that transcription of a noncoding RNA LRRK1-CAPT promoted LUSC cell proliferation, suggesting its oncogenic role. Our findings largely expand our understanding of cancer-associated transcription events, which may facilitate the development of novel strategies for cancer diagnosis and treatment.
Insights
Researchers discovered hundreds of cryptic antisense polyadenylated transcripts (CAPTs) in tumors, linked to cancer progression. These findings offer new avenues for cancer diagnosis and treatment strategies.
Area of Science:
- Genomics
- Cancer Biology
- Epigenetics
Background:
- Cryptic transcription initiation is linked to oncogenic transcript activation.
- The role of cryptic antisense transcription in cancer remains largely unexplored.
Purpose of the Study:
- To investigate the prevalence and impact of cryptic antisense transcription in cancer.
- To identify and characterize novel cryptic antisense polyadenylated transcripts (CAPTs).
Main Methods:
- Utilized a computational pipeline on public transcriptome and epigenome datasets.
- Analyzed chromatin accessibility and histone marks.
- Employed CRISPR-mediated epigenetic editing assays.
Main Results:
- Identified hundreds of unannotated CAPTs enriched in tumor samples.
- Found that cryptic antisense transcription correlates with increased chromatin accessibility and active histone marks.
- Demonstrated that LUSC cell proliferation is promoted by the noncoding RNA LRRK1-CAPT.
Conclusions:
- Cryptic antisense transcription is a prevalent and impactful event in cancer.
- CAPTs represent potential novel targets for cancer diagnosis and therapy.
- Epigenetic modifications play a role in the regulation of cryptic antisense transcription.
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