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Updated: Oct 24, 2025

Dual CRISPR-Interference Strategy for Targeting Synthetic Lethal Interactions Between Non-Coding RNAs in Cancer Cells
Published on: May 30, 2025
Keep your eyes peeled for long noncoding RNAs: Explaining their boundless role in cancer metastasis, drug resistance,
Ganesh Kumar Barik1, Osheen Sahay2, Abhayananda Behera3
1Cancer Biology Division, National Centre for Cell Science, Savitribai Phule Pune University, Ganeshkhind Road, Pune, Maharashtra 411007, India.
Abstract:
Cancer metastasis and drug resistance are two major obstacles in the treatment of cancer and therefore, the leading cause of cancer-associated mortalities worldwide. Hence, an in-depth understanding of these processes and identification of the underlying key players could help design a better therapeutic regimen to treat cancer. Earlier thought to be merely transcriptional junk and having passive or secondary function, recent advances in the genomic research have unravelled that long noncoding RNAs (lncRNAs) play pivotal roles in diverse physiological as well as pathological processes including cancer metastasis and drug resistance. LncRNAs can regulate various steps of the complex metastatic cascade such as epithelial-mesenchymal transition (EMT), invasion, migration and metastatic colonization, and also affect the sensitivity of cancer cells to various chemotherapeutic drugs. A substantial body of literature for more than a decade of research evince that lncRNAs can regulate gene expression at different levels such as epigenetic, transcriptional, posttranscriptional, translational and posttranslational levels, depending on their subcellular localization and through their ability to interact with DNA, RNA and proteins. In this review, we mainly focus on how lncRNAs affect cancer metastasis by modulating expression of key metastasis-associated genes at various levels of gene regulation. We also discuss how lncRNAs confer cancer cells either sensitivity or resistance to various chemo-therapeutic drugs via different mechanisms. Finally, we highlight the immense potential of lncRNAs as prognostic and diagnostic biomarkers as well as therapeutic targets in cancer.
Insights
Long noncoding RNAs (lncRNAs) are key regulators of cancer metastasis and drug resistance. Understanding lncRNA functions offers new therapeutic strategies for cancer treatment.
Area of Science:
- Molecular Biology
- Genomics
- Cancer Research
Background:
- Cancer metastasis and drug resistance are primary causes of cancer mortality.
- Long noncoding RNAs (lncRNAs), once considered transcriptional junk, are now recognized as critical regulators in cancer progression.
- lncRNAs influence key steps in metastasis and modulate cancer cell sensitivity to chemotherapy.
Purpose of the Study:
- To review the multifaceted roles of lncRNAs in cancer metastasis.
- To explore how lncRNAs impact cancer cell drug resistance.
- To highlight the potential of lncRNAs as biomarkers and therapeutic targets.
Main Methods:
- Literature review focusing on lncRNA regulation of gene expression.
- Analysis of lncRNA interactions with DNA, RNA, and proteins.
- Examination of lncRNA's role in epigenetic, transcriptional, and posttranscriptional regulation.
Main Results:
- lncRNAs modulate critical genes involved in epithelial-mesenchymal transition (EMT), invasion, migration, and colonization.
- lncRNAs influence cancer cell sensitivity or resistance to various chemotherapeutic agents through diverse mechanisms.
- lncRNAs function at multiple levels of gene regulation based on their localization and binding partners.
Conclusions:
- lncRNAs are pivotal in regulating cancer metastasis and drug resistance.
- lncRNAs offer significant potential as diagnostic and prognostic biomarkers for cancer.
- Targeting lncRNAs presents a promising therapeutic avenue for improving cancer treatment outcomes.
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