The Role of MicroRNA in DNA Damage Response

Li, Yongxin; Tong, Yan; Liu, Jiaqi; Lou, Jianlin

doi:10.3389/fgene.2022.850038

Cited by 8 publications

(10 citation statements)

References 60 publications

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“…A viral vector containing polymerase III promoters for steady miR recovery can be used to induce high transcription of these miRNAs from well-specified transcription starts and complementary regions, although they are not cell-specific. On the other hand, RNA polymerase II promoters can be used to produce miRNAs for a tissue-specific strategy or ectopic miRNA production ( Li Y. et al, 2022 ). In HNSCC, subsequent approaches, such as miR-375, can be used to effectively restore downregulated miRNAs.…”

Section: Mirnas As Emerging Novel Therapeutic Targets For Hnsccmentioning

confidence: 99%

“…Currently, host miRNAs are often silenced using antagomiRs (recently discovered chemically engineered oligonucleotides) ( Li Y. et al, 2022 ). When antagomir-155 was introduced into hairless mice, the effect of overexpression of miRNAs was reversed in HNSCC, resulting in decreased cellular proliferation and increased induction of apoptosis in KB cells transfected with miRNA-155.…”

Section: Mirnas As Emerging Novel Therapeutic Targets For Hnsccmentioning

confidence: 99%

“…By producing an mRNA with multiple tandem binding domains for the comprehensive group of certain miRNAs, miRNA sponges prevent some miRNAs from attaching to specific targets and exerting an effect. However, the miRNAs-masking antisense oligonucleotide technique, which consists of corresponding antisense oligonucleotides at the miRNA interaction site in the untranslated region of a targeted mRNA, shows its effect by disrupting the relationship between specific miR-mRNA pairings ( Li Y. et al, 2022 ). Due to the sequential targeting of numerous pathways, this technology offers an advantage over others in that there are fewer off-target or undesirable consequences.…”

Section: Mirnas As Emerging Novel Therapeutic Targets For Hnsccmentioning

confidence: 99%

“…To achieve this goal, it is necessary to target miRNA biogenesis devices or regulatory pathways. However, it is strongly advisable to explore the full power of these drugs ( Li Y. et al, 2022 ).…”

Section: Mirnas As Emerging Novel Therapeutic Targets For Hnsccmentioning

confidence: 99%

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Pharmacological impact of microRNAs in head and neck squamous cell carcinoma: Prevailing insights on molecular pathways, diagnosis, and nanomedicine treatment

Bhattacharjee¹,

Syeda

Rynjah³

et al. 2023

Front. Pharmacol.

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Head and neck squamous cell carcinoma is a disease that most commonly produce tumours from the lining of the epithelial cells of the lips, larynx, nasopharynx, mouth, or oro-pharynx. It is one of the most deadly forms of cancer. About one to two percent of all neo-plasm-related deaths are attributed to head and neck squamous cell carcinoma, which is responsible for about six percent of all cancers. MicroRNAs play a critical role in cell proliferation, differentiation, tumorigenesis, stress response, triggering apoptosis, and other physiological process. MicroRNAs regulate gene expression and provide new diagnostic, prognostic, and therapeutic options for head and neck squamous cell carcinoma. In this work, the role of molecular signaling pathways related to head and neck squamous cell carcinoma is emphasized. We also provide an overview of MicroRNA downregulation and overexpression and its role as a diagnostic and prognostic marker in head and neck squamous cell carcinoma. In recent years, MicroRNA nano-based therapies for head and neck squamous cell carcinoma have been explored. In addition, nanotechnology-based alternatives have been discussed as a promising strategy in exploring therapeutic paradigms aimed at improving the efficacy of conventional cytotoxic chemotherapeutic agents against head and neck squamous cell carcinoma and attenuating their cytotoxicity. This article also provides information on ongoing and recently completed clinical trials for therapies based on nanotechnology.

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Section: Mirnas As Emerging Novel Therapeutic Targets For Hnsccmentioning

confidence: 99%

Section: Mirnas As Emerging Novel Therapeutic Targets For Hnsccmentioning

confidence: 99%

Section: Mirnas As Emerging Novel Therapeutic Targets For Hnsccmentioning

confidence: 99%

Section: Mirnas As Emerging Novel Therapeutic Targets For Hnsccmentioning

confidence: 99%

See 2 more Smart Citations

Pharmacological impact of microRNAs in head and neck squamous cell carcinoma: Prevailing insights on molecular pathways, diagnosis, and nanomedicine treatment

Bhattacharjee¹,

Syeda

Rynjah³

et al. 2023

Front. Pharmacol.

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“…Various miRNAs regulate the expression of DNA damage proteins leading to genomic instability ( 384 ). However, little is known regarding the role of the miR-200 family in the regulation of genomic instability and mutations.…”

Section: Genome Instability and Mutationsmentioning

confidence: 99%

The role of miR-200 family in the regulation of hallmarks of cancer

et al. 2022

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MiRNAs are short non-coding RNAs that regulate gene expression post-transcriptionally contributing to the development of different diseases including cancer. The miR-200 family consists of five members, miR-200a, miR-200b, miR-200c, miR-141, and miR-429. Their expression is dysregulated in cancer tissue and their level is altered in the body fluids of cancer patients. Moreover, the levels of miR-200 family members correlate with clinical parameters such as cancer patients’ survival which makes them potentially useful as diagnostic and prognostic biomarkers. MiRNAs can act as either oncomiRs or tumor suppressor miRNAs depending on the target genes and their role in the regulation of key oncogenic signaling pathways. In most types of cancer, the miR-200 family acts as tumor suppressor miRNA and regulates all features of cancer. In this review, we summarized the expression pattern of the miR-200 family in different types of cancer and their potential utility as biomarkers. Moreover, we comprehensively described the role of miR-200 family members in the regulation of all hallmarks of cancer proposed by Hanahan and Weinberg with the focus on the epithelial-mesenchymal transition, invasiveness, and metastasis of tumor cells.

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TATDN2 resolution of R-loops is required for survival of BRCA1-mutant cancer cells

Jaiswal,

Dutta,

Srinivasan

et al. 2023

Nucleic Acids Research

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BRCA1-deficient cells have increased IRE1 RNase, which degrades multiple microRNAs. Reconstituting expression of one of these, miR-4638–5p, resulted in synthetic lethality in BRCA1-deficient cancer cells. We found that miR-4638-5p represses expression of TATDN2, a poorly characterized member of the TATD nuclease family. We discovered that human TATDN2 has RNA 3′ exonuclease and endonuclease activity on double-stranded hairpin RNA structures. Given the cleavage of hairpin RNA by TATDN2, and that BRCA1-deficient cells have difficulty resolving R-loops, we tested whether TATDN2 could resolve R-loops. Using in vitro biochemical reconstitution assays, we found TATDN2 bound to R-loops and degraded the RNA strand but not DNA of multiple forms of R-loops in vitro in a Mg2+-dependent manner. Mutations in amino acids E593 and E705 predicted by Alphafold-2 to chelate an essential Mg2+ cation completely abrogated this R-loop resolution activity. Depleting TATDN2 increased cellular R-loops, DNA damage and chromosomal instability. Loss of TATDN2 resulted in poor replication fork progression in the presence of increased R-loops. Significantly, we found that TATDN2 is essential for survival of BRCA1-deficient cancer cells, but much less so for cognate BRCA1-repleted cancer cells. Thus, we propose that TATDN2 is a novel target for therapy of BRCA1-deficient cancers.

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The Role of MicroRNA in DNA Damage Response

Cited by 8 publications

References 60 publications

Pharmacological impact of microRNAs in head and neck squamous cell carcinoma: Prevailing insights on molecular pathways, diagnosis, and nanomedicine treatment

Pharmacological impact of microRNAs in head and neck squamous cell carcinoma: Prevailing insights on molecular pathways, diagnosis, and nanomedicine treatment

The role of miR-200 family in the regulation of hallmarks of cancer

TATDN2 resolution of R-loops is required for survival of BRCA1-mutant cancer cells

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