ArticlePLoS genetics2018
A natural antisense lncRNA controls breast cancer progression by promoting tumor suppressor gene mRNA stability.
Article in PLoS genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers.
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Who cites it
88 citing papers in PubMed, 141 citations in OpenAlex.
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- Comprehensive Transcriptome Analysis Expands lncRNA Functional Profiles in Breast Cancer.International journal of molecular sciences · 2024Article
- How antisense transcripts can evolve to encode novel proteins.Nature communications · 2024Article
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- Beyond the Genome: Deciphering the Role of MALAT1 in Breast Cancer Progression.Current genomics · 2024Review
- The impact of ferroptosis and ferroptosis-related non-coding RNAs on breast cancer progression.Frontiers in cell and developmental biology · 2024Review
- Regulatory Roles of Long Non-Coding RNAs Relevant to Antioxidant Enzymes and Immune Responses ofInternational journal of molecular sciences · 2023Article
- Long Non-Coding RNAs and Their "Discrete" Contribution to IBD and Johne's Disease-What Stands out in the Current Picture? A Comprehensive Review.International journal of molecular sciences · 2023Review
- Discovery of long non-coding RNAs in the liver fluke, Fasciola hepatica.PLoS neglected tropical diseases · 2023Article
- A Co-Expressed Natural Antisense RNAMicrobiology spectrum · 2023Article
28 more citing papers are in PubMed but not listed here.
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Authors and funding
18 authors at 3 institutions in 1 country.
Funding
Abstract
The human genome encodes thousands of long noncoding RNA (lncRNA) genes; the function of majority of them is poorly understood. Aberrant expression of a significant number of lncRNAs is observed in various diseases, including cancer. To gain insights into the role of lncRNAs in breast cancer progression, we performed genome-wide transcriptome analyses in an isogenic, triple negative breast cancer (TNBC/basal-like) progression cell lines using a 3D cell culture model. We identified significantly altered expression of 1853 lncRNAs, including ~500 natural antisense transcript (NATs) lncRNAs. A significant number of breast cancer-deregulated NATs displayed co-regulated expression with oncogenic and tumor suppressor protein-coding genes in cis. Further studies on one such NAT, PDCD4-AS1 lncRNA reveal that it positively regulates the expression and activity of the tumor suppressor PDCD4 in mammary epithelial cells. Both PDCD4-AS1 and PDCD4 show reduced expression in TNBC cell lines and in patients, and depletion of PDCD4-AS1 compromised the cellular levels and activity of PDCD4. Further, tumorigenic properties of PDCD4-AS1-depleted TNBC cells were rescued by exogenous expression of PDCD4, implying that PDCD4-AS1 acts upstream of PDCD4. Mechanistically, PDCD4-AS1 stabilizes PDCD4 RNA by forming RNA duplex and controls the interaction between PDCD4 RNA and RNA decay promoting factors such as HuR. Our studies demonstrate crucial roles played by NAT lncRNAs in regulating post-transcriptional gene expression of key oncogenic or tumor suppressor genes, thereby contributing to TNBC progression.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.