Functional Screening Techniques to Identify Long Non-Coding RNAs as Therapeutic Targets in Cancer

Lucere, Kathleen M; O'Malley, Megan M R; Diermeier, Sarah D.

doi:10.3390/cancers12123695

Cited by 13 publications

(8 citation statements)

References 122 publications

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“…Long non-coding RNA (lncRNA), non-coding RNA longer than 200 nucleotides, demonstrated important roles in carcinogenesis 16 , 17 . LncRNAs could modulate various biological functions by regulating mRNA expression through sponging miRNAs 18 , 19 .…”

Section: Introductionmentioning

confidence: 99%

NSE, positively regulated by LINC00657-miR-93-5p axis, promotes small cell lung cancer (SCLC) invasion and epithelial-mesenchymal transition (EMT) process

Lü¹,

Zha²,

Zhang³

et al. 2021

Int. J. Med. Sci.

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Background: Neuron specific enolase (NSE) is a specific biomarker for SCLC. However, the biological roles and aberrant expression of NSE in SCLC have not been well illustrated. Methods: The expression of NSE, miR-93-5p and LINC00657 in SCLC tissues and cell lines were detected using real time quantitative PCR (qRT-PCR) or immunohistochemistry. CCK8 assay was performed to detect cell proliferation. Cell migration and invasion capabilities were investigated by transwell assay. Epithelial-mesenchymal transition (EMT) process was verified by detecting epithelial marker E-cadherin and mesenchymal marker N-cadherin. The direct interactions between miR-93-5p and NSE or LINC00657 were predicted by bioinformatics tools and verified using dual luciferase reporter assay. Results: Upregulated expression of NSE in SCLC tumor tissues were positively associated with advanced tumor stage, distant metastasis and poor overall survival. Overexpression of NSE promoted cell proliferation, migration, invasion and EMT in SCLC cells, while silence of NSE inhibited these effects. Mechanically, NSE expression was positively correlated with LINC00657, and negatively correlated with miR-93-5p. Moreover, NSE was positively regulated by LINC00657 through sponging of miR-93-5p. LINC00657 and miR-93-5p promoted SCLC cell migration, invasion and EMT by NSE-mediated manner. Conclusion: Overall, our study revealed a novel role of NSE in SCLC. NSE was positively regulated by LINC00657 through competitively interacting with miR-93-5p, which may be potential targets for SCLC patients.

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Section: Introductionmentioning

confidence: 99%

NSE, positively regulated by LINC00657-miR-93-5p axis, promotes small cell lung cancer (SCLC) invasion and epithelial-mesenchymal transition (EMT) process

Lü¹,

Zha²,

Zhang³

et al. 2021

Int. J. Med. Sci.

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“…The CRISPR/Cas system has been applied in inherited diseases and neurodegenerative diseases. [ 7 , 13 , 27 ] However, few CRISPR systems are available for acute diseases, as represented by acute inflammatory diseases. [ 28 ] Under normal conditions, cytokines are produced and catabolized rapidly due to their short half‐life.…”

Section: Discussionmentioning

confidence: 99%

“…[ 6 ] CRISPR/Cas13d (CasRx) has high specificity and efficiency compared with the RNAi system, which supports its further development and widespread application. [ 6 , 7 ] However, no reports of the use of EVs to deliver CasRx to prevent or treat disease have been published.…”

Section: Introductionmentioning

confidence: 99%

Engineered Extracellular Vesicle‐Delivered CRISPR/CasRx as a Novel RNA Editing Tool

Zhang

et al. 2023

Advanced Science

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Engineered extracellular vesicles (EVs) are considered excellent delivery vehicles for a variety of therapeutic agents, including nucleic acids, proteins, drugs, and nanomaterials. Recently, several studies have indicated that clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR‐associated 9 (Cas9) delivered by EVs enable efficient DNA editing. However, an RNA editing tool delivered by EVs is still unavailable. Here, a signal peptide‐optimized and EVs‐delivered guide RNA (gRNA) and CRISPR/CasRx (Cas13d) system capable of rapidly inhibiting the expression of targeted genes with quick catabolism after performing their functions is developed. EVs with CRISPR/CasRx and tandem gRNAs targeting pivotal cytokines are further packed whose levels increase substantially over the course of acute inflammatory diseases and find that these engineered EVs inhibit macrophage activation in vitro. More importantly, this system attenuates lipopolysaccharide (LPS)‐triggered acute lung injury and sepsis in the acute phase, mitigating organ damage and improving the prognosis in vivo. In summary, a potent tool is provided for short‐acting RNA editing, which could be a powerful therapeutic platform for the treatment of acute diseases.

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“…Currently, there are three novel therapeutic strategies focusing on lncRNAs in osteosarcoma, including small interfering RNA (siRNA), an antisense oligonucleotide (ASO)-based strategies and molecular inhibitors, all of which modulate lncRNA expression by gene editing [ 168 ]. RNAi is an effective method to reduce the amount or activity of target lncRNA via several mechanisms.…”

Section: Potential Of Wnt-related Lncrnas As Biomarkers and Therapeutic Targets In Osteosarcomamentioning

confidence: 99%

Functional interplay between long non-coding RNAs and the Wnt signaling cascade in osteosarcoma

Lin

Liu

et al. 2021

Cancer Cell Int

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Osteosarcoma is a common and highly malignant bone tumor among children, adolescents and young adults. However, the underlying molecular mechanisms remain largely unexplored. LncRNAs are transcripts with no or limited protein-coding capacity in human genomes, and have been demonstrated to play crucial functions in initiation, progression, therapeutic resistance, recurrence and metastasis of tumor. Considerable studies revealed a dysregulated lncRNA expression pattern in osteosarcoma, which may act as oncogenes or suppressors to regulate osteosarcoma progression. Wnt signaling pathway is an important cascade in tumorigenesis by modulation of pleiotropic biological functions including cell proliferation, apoptosis, differentiation, stemness, genetic stability and chemoresistance. Hyperactivation or deficiency of key effectors in Wnt cascade is a common event in many osteosarcoma patients. Recently, increasing evidences have suggested that lncRNAs could interplay with component of Wnt pathway, and thereby contribute to osteosarcoma onset, progression and dissemination. In this review, we briefly summarize Wnt signaling-related lncRNAs in osteosarcoma progression, aiming to gain insights into their underlying crosstalk as well as clinical application in osteosarcoma therapeutic modalities.

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Functional Screening Techniques to Identify Long Non-Coding RNAs as Therapeutic Targets in Cancer

Cited by 13 publications

References 122 publications

NSE, positively regulated by LINC00657-miR-93-5p axis, promotes small cell lung cancer (SCLC) invasion and epithelial-mesenchymal transition (EMT) process

NSE, positively regulated by LINC00657-miR-93-5p axis, promotes small cell lung cancer (SCLC) invasion and epithelial-mesenchymal transition (EMT) process

Engineered Extracellular Vesicle‐Delivered CRISPR/CasRx as a Novel RNA Editing Tool

Functional interplay between long non-coding RNAs and the Wnt signaling cascade in osteosarcoma

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