CRISPR/Cas9-mediated noncoding RNA editing in human cancers

Yang, Jie; Meng, Xiaoxiao; Pan, Jinchang; Jiang, Nan; Zhou, Chengwei; Wu, Zhenhua; Gong, Zhaohui

doi:10.1080/15476286.2017.1391443

Cited by 89 publications

(60 citation statements)

References 94 publications

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“…Targeting ncRNAs with CRISPR/Cas9 has been reported in cancer [130]. Specifically, lncRNA UCA1 (urothelial carcinoma-associated 1), upregulated in bladder cancer, could be inhibited by transcript-specific CRISPR/Cas9-associated gRNAs (guide RNAs) in vitro and in vivo, demonstrating its potential therapeutic value [131].…”

Section: Therapeutic Targetsmentioning

confidence: 99%

The Missing Lnc: The Potential of Targeting Triple-Negative Breast Cancer and Cancer Stem Cells by Inhibiting Long Non-Coding RNAs

Brown

Wasson

Marcato

2020

Cells

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Treatment decisions for breast cancer are based on staging and hormone receptor expression and include chemotherapies and endocrine therapy. While effective in many cases, some breast cancers are resistant to therapy, metastasize and recur, leading to eventual death. Higher percentages of tumor-initiating cancer stem cells (CSCs) may contribute to the increased aggressiveness, chemoresistance, and worse outcomes among breast cancer. This may be particularly true in triple-negative breast cancers (TNBCs) which have higher percentages of CSCs and are associated with worse outcomes. In recent years, increasing numbers of long non-coding RNAs (lncRNAs) have been identified as playing an important role in breast cancer progression and some of these have been specifically associated within the CSC populations of breast cancers. LncRNAs are non-protein-coding transcripts greater than 200 nucleotides which can have critical functions in gene expression regulation. The preclinical evidence regarding lncRNA antagonists for the treatment of cancer is promising and therefore, presents a potential novel approach for treating breast cancer and targeting therapy-resistant CSCs within these tumors. Herein, we summarize the lncRNAs that have been identified as functionally relevant in breast CSCs. Furthermore, our review of the literature and analysis of patient datasets has revealed that many of these breast CSC-associated lncRNAs are also enriched in TNBC. Together, this suggests that these lncRNAs may be playing a particularly important role in TNBC. Thus, certain breast cancer-promoting/CSC-associated lncRNAs could be targeted in the treatment of TNBCs and the CSCs within these tumors should be susceptible to anti-lncRNA therapy.

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Section: Therapeutic Targetsmentioning

confidence: 99%

The Missing Lnc: The Potential of Targeting Triple-Negative Breast Cancer and Cancer Stem Cells by Inhibiting Long Non-Coding RNAs

Brown

Wasson

Marcato

2020

Cells

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“…CRISPR-mediated gene editing is a powerful technology that has been successfully used to knock out specific lncRNAs and circRNAs [31][32][33][34]. We therefore sought to use this approach to knock out CDR1as in 293 T cells, using two sgRNAs targeting the CDR1 locus containing the CDR1as sequence (Fig.…”

Section: Crispr-mediated Generation Of Cdr1as Crispri Cell Linesmentioning

confidence: 99%

The circular RNA CDR1as regulate cell proliferation via TMED2 and TMED10

Yang

et al. 2020

BMC Cancer

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Background: Circular RNAs (CircRNAs) are biologically active RNAs. CDR1as is one such circRNA previously reported to be a microRNA-7 (miR-7) sponge, thereby regulating associated gene expression. The specific underlying molecular mechanisms of CDR1as biology, however, remain largely unknown. Methods: We performed CDR1as knockdown in order to explore its function in cell proliferation, migration, the cell cycle, and tumorigenesis. We further employed quantitative proteomic analyses and associated bioinformatics strategies to globally assess CDR1as-regulated proteins (CRPs). Western blotting and immunofluorescence staining were used to validate the proteomic results. We additionally investigated a specific link between TMED2, TMED10, and miR-7 via a dual-luciferase reporter system, and generated CDR1as knockout cell lines via CRISPR/Cas9 editing. Results: We identified 353 proteins dysregulated upon CDR1as knockdown in 293 T cells. These CRPs were found to interact with one another and to play key roles in certain cellular pathways. Two such proteins, TMED2 and TMED10, were found to specifically contribute to the influence of CDR1as on cell proliferation. CDR1as may regulate these two TMED proteins through miR-7 sponging. We were able to further confirm these results using both CRISPRi cell lines and nude mouse models. Conclusion: This study suggested that CDR1as may regulate cell proliferation via serving as a miR-7 sponge, thereby regulating TMED2 and TMED10 expression. These results are an invaluable template for future streamlined studies of circRNAs.

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“…A limitation to apply CRISPR/Cas9 system to noncoding genes is that tiny indels may not necessarily generate a functional loss of a specific noncoding gene and the most protocols can perform small point mutations; plus not all lncRNAs CRISPR can be applied. Another limitation is that, although it is more specific than other systems, this technique may still have off-target effects [76,77].…”

Section: Clinical Application For Lncrnasmentioning

confidence: 99%

lncRNAs in Hallmarks of Cancer and Clinical Applications

Garcia¹,

Zambalde²,

Mathias³

et al. 2020

Non-Coding RNAs

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Long noncoding RNAs (lncRNAs) are transcripts longer than 200 nucleotides in length that, in general, do not appear to have protein-coding potential. lncRNAs act in gene regulation involved with several biological processes. Furthermore, lncRNAs have been associated with a significant number of cancers, suggesting a potential role in tumorigenesis and progression. For example, HOTAIR regulates proliferation processes and other lncRNAs like highly upregulated in liver cancer (HULC), H19, PTENP1, HEIH, and antisense noncoding RNA in the INK4 locus (ANRIL). Other lncRNAs as AFAP1-AS1 and lincRNA-p21 can interact with BCL-2 and TP53, acting in apoptosis. Moreover, NORAD plays a vital role in genomic stability. Additionally, due to deregulated expression and high tissue specificity level, lncRNAs exhibit great potential as prognostic markers. In this chapter, we review the most highlighted lncRNAs acting in hallmarks of cancer and clinical application.

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CRISPR/Cas9-mediated noncoding RNA editing in human cancers

Cited by 89 publications

References 94 publications

The Missing Lnc: The Potential of Targeting Triple-Negative Breast Cancer and Cancer Stem Cells by Inhibiting Long Non-Coding RNAs

The Missing Lnc: The Potential of Targeting Triple-Negative Breast Cancer and Cancer Stem Cells by Inhibiting Long Non-Coding RNAs

The circular RNA CDR1as regulate cell proliferation via TMED2 and TMED10

lncRNAs in Hallmarks of Cancer and Clinical Applications

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