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Emerging roles of PIWI-interacting RNAs in cancer molecular diagnostics and therapeutics: a molecular biosciences
Qianqian Yang1, Jingping Wu2, Yu Su3
1Clinical Medical College, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China.
Abstract:
Cancer claims nearly 10 million lives yearly, demanding innovative diagnostics and therapies beyond surgery and chemotherapy's limitations, such as resistance and toxicity. Next-generation sequencing has unveiled PIWI-interacting RNAs (piRNAs), 26-31 nucleotide small non-coding RNAs, as pivotal regulators in cancer pathogenesis, offering fresh biomarkers and targets from a molecular biosciences lens. Once deemed germline-exclusive for transposon silencing via PIWI proteins (PIWIL1-4), piRNAs exhibit somatic dysregulation across malignancies, driving hallmarks like proliferation, metastasis, and chemoresistance. In colorectal cancer, piR-823 fosters invasion by stabilizing HIF-1α and G6PD, correlating with poor prognosis. Gastric cancers overexpress piR-651, promoting G2/M arrest evasion; lung cancers feature PMLCPIR enhancing ITGB1-PI3K-AKT signaling; multiple myeloma leverages piR-823 for proliferation; and hepatocellular carcinoma shows PIWIL1 upregulation tied to stemness. PiRNAs' tissue-specific signatures enable liquid biopsy detection, with panels predicting recurrence-free survival (e.g., piR-54265/STAT3 axis in CRC). Therapeutically, piRNA mimics/inhibitors (e.g., LNA-antisense against piR-L-138 in lung squamous cell carcinoma) sensitize tumors to cisplatin, while PIWI knockdown curbs metastasis preclinically. This review dissects piRNA biogenesis, oncogenic/suppressive duality, and translational promise. By bridging molecular mechanisms to clinical utility, encompassing diagnostics via plasma profiling and therapeutics like nanoparticle-delivered piRNA therapeutics, piRNAs herald a paradigm shift in precision oncology.
Insights
PIWI-interacting RNAs (piRNAs) are small non-coding RNAs crucial in cancer development and progression. These molecules show promise as novel biomarkers for early detection and as therapeutic targets for precision oncology treatments.
Area of Science:
- Molecular Biosciences
- Oncology
- Genomics
Background:
- Cancer necessitates advanced diagnostics and therapies due to limitations of current treatments like surgery and chemotherapy.
- PIWI-interacting RNAs (piRNAs), small non-coding RNAs, are increasingly recognized as key regulators in cancer pathogenesis.
- Dysregulation of piRNAs is observed across various malignancies, influencing cancer hallmarks such as proliferation, metastasis, and chemoresistance.
Purpose of the Study:
- To review the role of piRNAs in cancer, covering their biogenesis, dual function (oncogenic and suppressive), and translational potential.
- To highlight piRNAs as promising biomarkers for cancer diagnostics and prognostics, particularly through liquid biopsies.
- To explore the therapeutic applications of piRNAs in precision oncology.
Main Methods:
- Literature review of studies on piRNA biogenesis, function, and clinical applications in cancer.
- Analysis of next-generation sequencing data implicating piRNAs in cancer pathogenesis.
- Examination of preclinical and clinical research on piRNA-based diagnostics and therapeutics.
Main Results:
- piRNAs are dysregulated in various cancers (colorectal, gastric, lung, multiple myeloma, hepatocellular carcinoma), impacting key oncogenic pathways.
- Tissue-specific piRNA signatures can be detected in liquid biopsies for early diagnosis and recurrence prediction.
- piRNA-based therapeutics (mimics, inhibitors) and PIWI targeted approaches show preclinical promise in sensitizing tumors and inhibiting metastasis.
Conclusions:
- piRNAs represent a significant advancement in molecular biosciences for understanding and combating cancer.
- The diagnostic and therapeutic potential of piRNAs offers a new frontier in precision oncology.
- Further research into piRNA mechanisms and clinical translation is crucial for realizing their full impact on cancer care.
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