How Non-Coding RNAs Are Revolutionizing Cancer Treatment
Exploring Dr. Ahmed Elbediwy's groundbreaking research on non-coding RNAs and their role in cancer signaling pathways
In the intricate landscape of human biology, a remarkable discovery has shifted our understanding of genetic regulation: the vast world of non-coding RNAs. Once dismissed as mere "junk DNA," these molecular players are now recognized as crucial regulators of gene expression, holding particular significance in cancer biology.
New breast cancer cases globally in 2020
Attributed deaths from breast cancer
Expected increase in endometrial cancer by 2045
Dr. Ahmed Elbediwy, an award-winning Senior Lecturer and Course Leader for BSc Biochemistry at Kingston University, stands at the forefront of this research, investigating how these microscopic elements influence female cancers that affect millions worldwide 6 . His work bridges the gap between fundamental cellular processes and therapeutic applications, offering new hope for targeted cancer treatments that could circumvent the limitations of conventional therapies.
"The exploration of non-coding RNAs represents a paradigm shift in oncology, revealing a hidden layer of genetic control that could unlock personalized approaches to cancer treatment."
For decades, the central dogma of molecular biology emphasized protein-coding genes as the primary actors in cellular function. However, recent advances have revealed that a surprisingly small fraction of our genome—less than 2%—actually codes for proteins. The remainder, once considered genetic "dark matter," produces a diverse array of non-coding RNAs (ncRNAs) that play crucial regulatory roles without being translated into proteins 1 .
These ncRNAs constitute approximately 98% of genomic output, forming an intricate network of molecules that fine-tune gene expression through multiple mechanisms 1 . Dr. Elbediwy's research focuses on deciphering this complex regulatory system, particularly its implications for cancer development and progression.
Non-coding RNAs exhibit a fascinating dual functionality in cancer biology, acting as either oncogenes or tumor suppressors depending on their expression levels and cellular context 1 3 . Certain ncRNAs, when overexpressed, can drive cancer progression by silencing tumor suppressor genes or activating growth pathways.
| Category | Subtype | Length | Primary Function | Role in Cancer |
|---|---|---|---|---|
| Housekeeping | rRNA | Varies | Ribosome structure; protein synthesis | Hijacked for increased protein production in cancer cells |
| tRNA | 70-90 nt | Delivering amino acids during translation | Source of tRNA-derived small RNAs (tsRNAs) linked to chemoresistance | |
| Regulatory | miRNA | 20-22 nt | Post-transcriptional gene silencing | Both oncogenic (oncomiRs) and tumor suppressive functions |
| siRNA | 20-25 nt | Transcriptional gene silencing | Emerging therapeutic applications in cancer | |
| piRNA | 26-31 nt | Silencing transposable elements | Potential biomarkers for cancer detection | |
| lncRNA | >200 nt | Chromatin remodeling, transcriptional regulation | Key regulators of oncogenic pathways |
Dr. Elbediwy's research focuses on how non-coding RNAs regulate established signaling transduction pathways that are commonly altered in cancer, including the MAPK, PI3K/Akt/mTOR, Wnt/β-catenin, and p53 pathways 1 3 . These pathways represent critical communication networks that control fundamental cellular processes such as proliferation, differentiation, survival, and death.
Regulates cell proliferation, differentiation, and survival. Dysregulation contributes to uncontrolled growth in many cancers.
Central role in cell growth and metabolism. Frequently mutated in cancers, leading to sustained proliferative signaling.
Controls embryonic development and cell stemness. Aberrant activation promotes cancer stem cell properties.
Serves as a crucial guardian against genomic instability. Mutated in over 50% of all human cancers.
| Pathway | Role in Cancer | Regulating ncRNAs | Cancer Types Affected |
|---|---|---|---|
| MAPK | Cell proliferation, differentiation, survival | miR-125b, MALAT1, GAS5 | Breast, ovarian, endometrial |
| PI3K/Akt/mTOR | Cell growth, metabolism, angiogenesis | miR-21, LINP1, NEAT1 | Breast, cervical, ovarian |
| Wnt/β-catenin | Embryonic development, cell stemness | miR-15a, CCAT2, H19 | Breast, endometrial, cervical |
| p53 | Genome stability, apoptosis, tumor suppression | miR-504, PANDA, GUARDIN | Breast, ovarian, cervical |
In an innovative approach to understanding breast cancer heterogeneity, Dr. Elbediwy and colleagues employed machine learning algorithms to investigate the association between insulin resistance and breast cancer progression 5 . Their study analyzed data from a large patient cohort comprising 6,907 BC samples across 10 cohorts, including TCGA-BRCA and METABRIC datasets 5 .
Insulin resistance-related genes (IRGs) identified from GeneCards database with relevance scores > 3.0
Identified seven hub genes with non-zero coefficients for inclusion in a prognostic model
The study yielded a robust prognostic model based on the seven-gene signature, which demonstrated remarkable predictive power across multiple validation cohorts 5 . Patients stratified into high- and low-IRRS groups showed significant differences in clinical outcomes.
| Cohort | Sample Size | HR (High vs. Low IRRS) | 95% CI | p-value |
|---|---|---|---|---|
| TCGA-BRCA (Training) | 1,095 | 2.41 | 1.87-3.11 | <0.001 |
| METABRIC | 1,906 | 1.89 | 1.56-2.29 | <0.001 |
| GSE96058 | 3,069 | 1.74 | 1.51-2.01 | <0.001 |
| GSE20685 | 327 | 2.02 | 1.38-2.95 | <0.001 |
| GSE7390 | 198 | 1.97 | 1.29-3.01 | 0.002 |
Cutting-edge cancer research relies on a sophisticated array of reagents and technologies that enable scientists to probe the molecular mechanisms of disease. Dr. Elbediwy's investigations into non-coding RNAs and signaling pathways employ several crucial experimental tools.
| Reagent/Technology | Function | Application Examples |
|---|---|---|
| RNA sequencing | Transcriptome profiling | Identification of dysregulated ncRNAs in cancer tissues |
| CRISPR-Cas9 | Gene editing | Functional validation of ncRNA roles in oncogenic pathways |
| Small molecule inhibitors | Targeted pathway inhibition | proTAME for APC/C inhibition in bladder cancer |
| siRNA/antisense oligonucleotides | Gene silencing | Knockdown of oncogenic ncRNAs (e.g., oncomiRs) |
| ncRNA mimics | Replacement therapy | Restoration of tumor-suppressive ncRNA function |
| Molecular docking software | Predicting ligand-target interactions | Analysis of drug binding to MMP2/MMP9 |
| Machine learning algorithms | Pattern recognition, prediction | Development of prognostic signatures based on IRGs 5 |
Essential for confirming computational predictions and establishing causal relationships
Critical for analyzing large datasets and identifying significant patterns
Reveals complex interactions between ncRNAs and their target pathways
The growing understanding of ncRNA biology has paved the way for developing novel therapeutic strategies that could complement or even replace conventional cancer treatments. Several approaches show particular promise, including antisense oligonucleotides that inhibit oncogenic ncRNAs, ncRNA mimics that restore tumor-suppressive functions, and small molecules that modulate ncRNA expression or activity.
Identification of dysregulated ncRNAs in various cancer types and understanding their mechanisms of action
Testing ncRNA-based therapeutics in cell cultures and animal models to establish efficacy and safety
Several ncRNA-based therapeutics are currently in various phases of clinical trials for cancer treatment
Personalized ncRNA therapies based on individual tumor profiles and combination approaches with existing treatments
Dr. Elbediwy's contributions extend beyond the laboratory to the classroom, where he emphasizes academic-led motivation and inclusive, student-centred teaching 6 . He recognizes that many contemporary students balance academic responsibilities with external pressures including work, caregiving, and family obligations.
The investigation of non-coding RNAs in cancer biology represents a paradigm shift in our understanding of gene regulation and cellular signaling. Once considered genomic "junk," these molecules are now recognized as master regulators of oncogenic pathways with profound implications for cancer development, progression, and treatment response.
Dr. Ahmed Elbediwy's research has contributed to this evolving landscape, particularly in elucidating how ncRNAs influence key signaling pathways in breast and gynecological cancers. His interdisciplinary approach—bridging computational biology, molecular techniques, and educational innovation—exemplifies the multifaceted strategies needed to advance cancer research.
As the field continues to evolve, ncRNA-based diagnostics and therapeutics hold immense promise for personalizing cancer treatment. Through the continued efforts of researchers like Dr. Elbediwy, the hidden world of non-coding RNAs may soon yield powerful new weapons in the fight against cancer.