Long non-coding RNA-targeting therapeutics: discovery and development update

Khorkova, Olga; Stahl, Jack; Joji, Aswathy; Volmar, Claude‐Henry; Zeier, Zane; Wahlestedt, Claes

doi:10.1080/17460441.2023.2236552

Cited by 11 publications

(5 citation statements)

References 134 publications

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“…In addition, RNA-targeted therapeutics are being developed to modulate the levels or functions of non-coding RNAs associated with cancer progression and metastasis ( 60 ). Epigenetic-targeted agents have demonstrated clinical activities in hematological malignancies and have shown therapeutic potential in solid tumors ( 61 ). The most notable advances are seen with DNMTis and HDACis, some of which have already been approved by the FDA for specific malignancies.…”

Section: Therapeutic Strategies Targeting Epigenetic Modificationsmentioning

confidence: 99%

“…These include DNA methyltransferase inhibitors (DNMTis), histone deacetylase inhibitors (HDACis), and histone methyltransferase inhibitors (HMTis), among others (59). In addition, RNA-targeted therapeutics are being developed to modulate the levels or functions of non-coding RNAs associated with cancer progression and metastasis (60). Epigenetic-targeted agents have demonstrated clinical activities in hematological malignancies and have shown therapeutic potential in solid tumors (61).…”

Section: Therapeutic Strategies Targeting Epigenetic Modificationsmentioning

confidence: 99%

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Epigenetic modifications in solid tumor metastasis in people of African ancestry

Oladipo,

Olufemi,

Adediran

et al. 2024

Front. Oncol.

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This review focuses on the critical role of epigenetic modifications in solid tumor metastasis, particularly in people of African ancestry. Epigenetic alterations, such as DNA methylation, histone modifications, alterations in non-coding RNAs, and mRNA methylation, significantly influence gene expression, contributing to cancer development and progression. Despite the primary focus on populations of European, American, and Asian descent in most cancer research, this work emphasizes the importance of studying the unique genetic and epigenetic landscapes of African populations for a more inclusive approach in understanding and treating cancer. Insights from this review have the potential to pave the way for the development of effective, tailored treatments, and provide a richer resource for understanding cancer progression and metastasis. Specific focus was placed on the role of DNA methylation, histone modifications, non-coding RNAs, and mRNA methylation in solid tumor metastasis, including how these modifications contribute to the regulation of tumor suppressor genes and oncogenes, influence cellular pathways and signaling, and interact with the immune system. Moreover, this review elaborates on the development of epigenetic-targeted therapeutic strategies and the current advances in this field, highlighting the promising applications of these therapies in improving outcomes for African ancestry populations disproportionately affected by certain types of cancer. Nevertheless, this work acknowledges the challenges that lie ahead, particularly the under-representation of African populations in cancer genomic and epigenomic studies and the technical complications associated with detecting subtle epigenetic modifications. Emphasis is placed on the necessity for more inclusive research practices, the development of more robust and sensitive methods for detecting and interpreting epigenetic changes, and the understanding of the interplay between genetic and epigenetic variations. The review concludes with an optimistic outlook on the future of epigenetic research in People of African ancestry, urging the concerted efforts of researchers, clinicians, funding agencies, and policymakers to extend the benefits of this research to all populations.

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Section: Therapeutic Strategies Targeting Epigenetic Modificationsmentioning

confidence: 99%

Section: Therapeutic Strategies Targeting Epigenetic Modificationsmentioning

confidence: 99%

Epigenetic modifications in solid tumor metastasis in people of African ancestry

Oladipo,

Olufemi,

Adediran

et al. 2024

Front. Oncol.

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“…For example, analyzing gene expression patterns in tumor samples can tailor personalized treatment plans for cancer patients. In summary, biobanks play an indispensable role in modern biomedical research, and with technological advancements, their application and impact are expected to further expand [ [33] , [34] , [35] ].…”

Section: Application Of Biobanks In Chronic Disease Researchmentioning

confidence: 99%

Biobanks in chronic disease management: A comprehensive review of strategies, challenges, and future directions

Xu,

Liang,

Chen

et al. 2024

Heliyon

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“…LncRNAs are appealing drug targets because they tend to have tightly regulated expression in space and time, and appear to show low conservation between parasite and host [ 49 , 52 ]. These characteristics could imply a lower probability of off-target effects than protein-targeting drugs.…”

Section: Introductionmentioning

confidence: 99%

“…LncRNAs could also be targeted by oligonucleotide-based drugs, which have a much lower development cost than small-molecule based therapies [ 53 ]. However, this appeal is mitigated somewhat by difficulties in formulating and administering oligonucleotide drugs to specific locations in the target organism–most are not efficiently absorbed by the intestine so must be delivered parenterally [ 52 ].…”

Section: Introductionmentioning

confidence: 99%

Discovery of long non-coding RNAs in the liver fluke, Fasciola hepatica

McVeigh,

McCammick,

Robb

et al. 2023

PLoS Negl Trop Dis

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Long non-coding (lnc)RNAs are a class of eukaryotic RNA that do not code for protein and are linked with transcriptional regulation, amongst a myriad of other functions. Using a custom in silico pipeline we have identified 6,436 putative lncRNA transcripts in the liver fluke parasite, Fasciola hepatica, none of which are conserved with those previously described from Schistosoma mansoni. F. hepatica lncRNAs were distinct from F. hepatica mRNAs in transcript length, coding probability, exon/intron composition, expression patterns, and genome distribution. RNA-Seq and digital droplet PCR measurements demonstrated developmentally regulated expression of lncRNAs between intra-mammalian life stages; a similar proportion of lncRNAs (14.2%) and mRNAs (12.8%) were differentially expressed (p<0.001), supporting a functional role for lncRNAs in F. hepatica life stages. While most lncRNAs (81%) were intergenic, we identified some that overlapped protein coding loci in antisense (13%) or intronic (6%) configurations. We found no unequivocal evidence for correlated developmental expression within positionally correlated lncRNA:mRNA pairs, but global co-expression analysis identified five lncRNA that were inversely co-regulated with 89 mRNAs, including a large number of functionally essential proteases. The presence of micro (mi)RNA binding sites in 3135 lncRNAs indicates the potential for miRNA-based post-transcriptional regulation of lncRNA, and/or their function as competing endogenous (ce)RNAs. The same annotation pipeline identified 24,141 putative lncRNAs in F. gigantica. This first description of lncRNAs in F. hepatica provides an avenue to future functional and comparative genomics studies that will provide a new perspective on a poorly understood aspect of parasite biology.

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Long non-coding RNA-targeting therapeutics: discovery and development update

Cited by 11 publications

References 134 publications

Epigenetic modifications in solid tumor metastasis in people of African ancestry

Epigenetic modifications in solid tumor metastasis in people of African ancestry

Biobanks in chronic disease management: A comprehensive review of strategies, challenges, and future directions

Discovery of long non-coding RNAs in the liver fluke, Fasciola hepatica

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