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Crosstalk between Long Non-Coding RNA and Spliceosomal microRNA as a Novel Biomarker for Cancer
1Department of Genetics, The Hebrew University of Jerusalem, Jerusalem 91904, Israel.
Abstract:
Non-coding RNAs (ncRNAs) play diverse roles in regulating cellular processes and have been implicated in pathological conditions, including cancer, where interactions between ncRNAs play a role. Relevant here are (i) microRNAs (miRNAs), mainly known as negative regulators of gene expression in the cytoplasm. However, identification of miRNAs in the nucleus suggested novel nuclear functions, and (ii) long non-coding RNA (lncRNA) regulates gene expression at multiple levels. The recent findings of miRNA in supraspliceosomes of human breast and cervical cancer cells revealed new candidates of lncRNA targets. Here, we highlight potential cases of crosstalk between lncRNA and supraspliceosomal miRNA expressed from the same genomic region, having complementary sequences. Through RNA:RNA base pairing, changes in the level of one partner (either miRNA or lncRNA), as occur in cancer, could affect the level of the other, which might be involved in breast and cervical cancer. An example is spliceosomal mir-7704 as a negative regulator of the oncogenic lncRNA HAGLR. Because the expression of spliceosomal miRNA is cell-type-specific, the list of cis-interacting lncRNA:spliceosomal miRNA presented here is likely just the tip of the iceberg, and such interactions are likely relevant to additional cancers. We thus highlight the potential of lncRNA:spliceosomal miRNA interactions as novel targets for cancer diagnosis and therapies.
Insights
Interactions between long non-coding RNAs (lncRNAs) and nuclear microRNAs (miRNAs) may drive cancer progression. Targeting these lncRNA:miRNA interactions could offer new diagnostic and therapeutic strategies for various cancers.
Area of Science:
- Molecular Biology
- Genetics
- Cancer Research
Background:
- Non-coding RNAs (ncRNAs), including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), regulate cellular processes.
- ncRNAs are implicated in cancer pathogenesis, with emerging roles for nuclear miRNAs and lncRNAs.
- Recent findings identified miRNAs within supraspliceosomes in cancer cells, suggesting novel interactions.
Purpose of the Study:
- To highlight potential crosstalk between lncRNAs and nuclear miRNAs originating from the same genomic regions.
- To explore the role of these interactions in cancer, specifically breast and cervical cancers.
- To identify novel targets for cancer diagnosis and therapy.
Main Methods:
- Literature review and analysis of potential RNA:RNA interactions.
- Identification of cis-interacting lncRNA:spliceosomal miRNA pairs.
- Case study of mir-7704 regulating the oncogenic lncRNA HAGLR.
Main Results:
- Potential for RNA:RNA base pairing between co-expressed lncRNAs and nuclear miRNAs.
- Dysregulation of these interactions in cancer could impact gene expression.
- Identified mir-7704 as a negative regulator of the oncogenic lncRNA HAGLR.
Conclusions:
- lncRNA:nuclear miRNA interactions represent a novel regulatory mechanism in cancer.
- These interactions, exemplified by HAGLR and mir-7704, are likely relevant to multiple cancer types.
- Targeting lncRNA:nuclear miRNA crosstalk offers promising avenues for cancer therapy and diagnostics.
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