Shubham Sharma
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shubham-s04.bsky.social
Shubham Sharma
@shubham-s04.bsky.social
Post-Doctoral Fellow, Dept of Biological Sciences & Engineering, IIT Gandhinagar, India. EMBO Fellow, France.
#NucleicAcids #G4 #cancer #diagnosis #therapeutics
Big thanks to Prof. Bhaskar Datta and Dr.@dmonchaud.bsky.social for their mentorship and tireless efforts. Special thanks to @dmonchaud.bsky.social and his team (GATTACA) for awesome collaboration. Grateful to @embo.org and IITGN for financially supporting my visit to GATTACA lab at ICMUB. (9/9)
August 26, 2025 at 6:24 AM
Our results demonstrate the potential of these lncRNA G4s to be used as targets for therapeutic interventions. Unlike DNA-targeting ligands that risk collateral genomic damage, this approach hints at a safer and more selective anticancer strategy. (8/9)
August 26, 2025 at 6:24 AM
💡 Why does it matter?
This work is among the first to demonstrate that pharmacologically ironing out RNA G4s in lncRNAs might influence cancer cell biology. (7/9)
August 26, 2025 at 6:24 AM
✅ Inferred that perturbing lncRNA G4s using ad hoc molecular tools (pharmacomodulation) could selectively disrupt CRC cell homeostasis and inner functioning of lncRNAs—opening a novel therapeutic avenue for CRC. (6/9)
August 26, 2025 at 6:24 AM
✅ Here's the most exciting part: Instead of using G4 stabilisation (the usual route, but often induce genetic instability), we introduced an innovative anticancer strategy of G4 destabilization using PhpC (a prototype molecule for destabilizing G4s). (5/9)
August 26, 2025 at 6:24 AM
🔍 Key highlights:
✅ Identified parallel, stable, and intramolecular G4s within CRC-dysregulated lncRNAs, both in vitro and in CRC cells.
✅ Demonstrated—these G4s can be modulated in vitro—are targetable inside CRC cells using ad hoc molecular tools (PhpC & BRACO-19). (4/9)
August 26, 2025 at 6:24 AM
Our study uncovers one such vulnerability that could be exploited therapeutically: ability of certain lncRNAs dysregulated in CRC—LINC01589, MELTF-AS1, and UXT-AS1—to fold into RNA G-quadruplexes (G4s), which is suspected to play active roles in lncRNA functions. (3/9)
August 26, 2025 at 6:24 AM
🧬 What’s new?
Colorectal cancer (CRC) remains the second leading cause of cancer-related deaths worldwide, yet the molecular vulnerabilities driving its progression are far from fully understood. (2/9)
August 26, 2025 at 6:24 AM
Further, it imparts information concerning the established G4-binding capabilities of proteins that interact with the catalogued lncRNAs. 6/6
August 26, 2025 at 6:18 AM
It also affords insights into the subcellular localization of catalogued lncRNAs across diverse cell lines & undertakes an exhaustive meta-analysis of interaction partners (RNA and protein) linked to catalogued lncRNAs based on the most recent available data. 5/6
August 26, 2025 at 6:18 AM
This database integrates standalone G4-prediction tools empower users to critically assess, categorize, & compare G4-predictions for any given sequence. 4/6
August 26, 2025 at 6:18 AM
CanlncG4 database presents 17,666 experimentally-validated associations between 6,408 human lncRNAs (including their transcript variants) & 15 distinct types of human cancers: predicting their G4-forming potential & categorizing G4s into anticipated G4 types (2G, 3G, and 4G). 3/6
August 26, 2025 at 6:18 AM
Our database, CanlncG4, intricately curated using this dataset can be accessed at canlncg4.com. 2/6
CanLncG4
CanLncG4, an intricately curated repository, compiles experimentally validated associations between long non-coding RNAs (lncRNAs) and diverse human cancers, and their G4-forming potential. This resou...
canlncg4.com
August 26, 2025 at 6:18 AM