LncRNAs and their RBPs: How to influence the fate of stem cells?

Zhao, Cong; Xie, Wen; Zhu, Hecheng; Zhao, Ming; Liu, Weidong; Wu, Zhaoping; Wang, Lei; Zhu, Bin; Li, Shasha; Zhou, Yao; Jiang, Xingjun; Xu, Qiang; Ren, Chao

doi:10.1186/s13287-022-02851-x

Cited by 17 publications

(14 citation statements)

References 105 publications

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“…LncRNAs usually function in stem cells by binding to proteins [53][54][55][56]. Here, seventy-two proteins specifically bound to ESRG were screened out by RNA pull-down and mass spectrometry.…”

Section: Discussionmentioning

confidence: 99%

ESRG is critical to maintain the cell survival and self-renewal/pluripotency of hPSCs by collaborating with MCM2 to suppress p53 pathway

Li¹,

Liu²,

Liu³

et al. 2023

Int. J. Biol. Sci.

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The mechanisms of self-renewal and pluripotency maintenance of human pluripotent stem cells (hPSCs) have not been fully elucidated, especially for the role of those poorly characterized long noncoding RNAs (lncRNAs). ESRG is a lncRNA highly expressed in hPSCs, and its functional roles are being extensively explored in the field. Here, we identified that the transcription of ESRG can be directly regulated by OCT4, a key self-renewal factor in hPSCs. Knockdown of ESRG induces hPSC differentiation, cell cycle arrest, and apoptosis. ESRG binds to MCM2, a replication-licensing factor, to sustain its steady-state level and nuclear location, safeguarding error-free DNA replication. Further study showed that ESRG knockdown leads to MCM2 abnormalities, resulting in DNA damage and activation of the p53 pathway, ultimately impairs hPSC self-renewal and pluripotency, and induces cell apoptosis. In summary, our study suggests that ESRG , as a novel target of OCT4, plays an essential role in maintaining the cell survival and self-renewal/pluripotency of hPSCs in collaboration with MCM2 to suppress p53 signaling. These findings provide critical insights into the mechanisms underlying the maintenance of self-renewal and pluripotency in hPSCs by lncRNAs.

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Section: Discussionmentioning

confidence: 99%

ESRG is critical to maintain the cell survival and self-renewal/pluripotency of hPSCs by collaborating with MCM2 to suppress p53 pathway

Li¹,

Liu²,

Liu³

et al. 2023

Int. J. Biol. Sci.

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“…Researches had shown that lncRNA do not represent transcriptional noise. which played an essential role in tumors (34)(35)(36)(37). For example, autophagy-related lncRNA characteristics could accurately forecast the prognosis of patients with Bladder Cancer (38).…”

Section: Discussionmentioning

confidence: 99%

Identification of novel cuproptosis-related lncRNA signatures to predict the prognosis and immune microenvironment of breast cancer patients

et al. 2022

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BackgroundCuproptosis is a new modality of cell death regulation that is currently considered as a new cancer treatment strategy. Nevertheless, the prognostic predictive value of cuproptosis-related lncRNAs in breast cancer (BC) remains unknown. Using cuproptosis-related lncRNAs, this study aims to predict the immune microenvironment and prognosis of BC patients. and develop new therapeutic strategies that target the disease.MethodsThe Cancer Genome Atlas (TCGA) database provided the RNA-seq data along with the corresponding clinical and prognostic information. Univariate and multivariate Cox regression analyses were performed to acquire lncRNAs associated with cuproptosis to establish predictive features. The Kaplan-Meier method was used to calculate the overall survival rate (OS) in the high-risk and low-risk groups. High risk and low risk gene sets were enriched to explore functional discrepancies among risk teams. The mutation data were analyzed using the “MAFTools” r-package. The ties of predictive characteristics and immune status had been explored by single sample gene set enrichment analysis (ssGSEA). Last, the correlation between predictive features and treatment condition in patients with BC was analyzed. Based on prognostic risk models, we assessed associations between risk subgroups and immune scores and immune checkpoints. In addition, drug responses in at-risk populations were predicted.ResultsWe identified a set of 11 Cuproptosis-Related lncRNAs (GORAB-AS1, AC 079922.2, AL 589765.4, AC 005696.4, Cytor, ZNF 197-AS1, AC 002398.1, AL 451085.3, YTH DF 3-AS1, AC 008771.1, LINC 02446), based on which to construct the risk model. In comparison to the high-risk group, the low-risk patients lived longer (p < 0.001). Moreover, cuproptosis-related lncRNA profiles can independently predict prognosis in BC patients. The AUC values for receiver operating characteristics (ROC) of 1-, 3-, and 5-year risk were 0.849, 0.779, and 0.794, respectively. Patients in the high-risk group had lower OS than those in the low-risk group when they were divided into groups based on various clinicopathological variables. The tumor burden mutations (TMB) correlation analysis showed that high TMB had a worse prognosis than low-TMB, and gene mutations were found to be different in high and low TMB groups, such as PIK3CA (36% versus 32%), SYNE1 (4% versus 6%). Gene enrichment analysis indicated that the differential genes were significantly concentrated in immune-related pathways. The predictive traits were significantly correlated with the immune status of BC patients, according to ssGSEA results. Finally, high-risk patients showed high sensitivity in anti-CD276 immunotherapy and conventional chemotherapeutic drugs such as imatinib, lapatinib, and pazopanib.ConclusionWe successfully constructed of a cuproptosis-related lncRNA signature, which can independently predict the prognosis of BC patients and can be used to estimate OS and clinical treatment outcomes in BRCA patients. It will serve as a foundation for further research into the mechanism of cuproptosis-related lncRNAs in breast cancer, as well as for the development of new markers and therapeutic targets for the disease.

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“…LncRNAs are involved in a variety of pathological and physiological processes 25,26 . It is worth noting that lncRNAs can serve as both potential diagnostic/prognostic biomarkers and important therapeutic targets for bone‐related diseases 27–30 . In recent years, scholars have made progress in uncovering the role of lncRNAs in regulating periodontal bone homeostasis.…”

Section: Introductionmentioning

confidence: 99%

Long non‐coding RNA AC018926.2 regulates palmitic acid exposure‐compromised osteogenic potential of periodontal ligament stem cells via the ITGA2/FAK/AKT pathway

Sun

et al. 2023

Cell Proliferation

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Although obesity has been proposed as a risk factor for periodontitis, the influence of excessive fat accumulation on the development of periodontitis and periodontal recovery from disease remains largely unknown. This study investigated the cellular response of periodontal ligament stem cells (PDLSCs) to elevated levels of a specific fatty acid, namely, palmitic acid (PA). The mechanism by which PA exposure compromises the osteogenic potential of cells was also explored. It was found that exposure of PDLSCs to abundant PA led to decreased cell osteogenic differentiation. Given that long non‐coding RNAs (lncRNAs) play a key role in the stem cell response to adverse environmental stimuli, we screened the lncRNAs that were differentially expressed in PDLSCs following PA exposure using lncRNA microarray analysis, and AC018926.2 was identified as the lncRNA that was most sensitive to PA. Next, gain/loss‐of‐function studies illustrated that AC018926.2 was an important regulator in PA‐mediated osteogenic differentiation of PDLSCs. Mechanistically, AC018926.2 upregulated integrin α2 (ITGA2) expression and therefore activated ITGA2/FAK/AKT signalling. Further functional studies revealed that inactivation of ITGA2/FAK/AKT signalling by silencing ITGA2 counteracted the pro‐osteogenic effect induced by AC018926.2 overexpression. Moreover, the results of bioinformatics analysis and RNA immunoprecipitation assay suggested that AC018926.2 might transcriptionally regulate ITGA2 expression by binding to PARP1 protein. Our data suggest that AC018926.2 may serve as a therapeutic target for the management of periodontitis in obese patients.

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LncRNAs and their RBPs: How to influence the fate of stem cells?

Cited by 17 publications

References 105 publications

ESRG is critical to maintain the cell survival and self-renewal/pluripotency of hPSCs by collaborating with MCM2 to suppress p53 pathway

ESRG is critical to maintain the cell survival and self-renewal/pluripotency of hPSCs by collaborating with MCM2 to suppress p53 pathway

Identification of novel cuproptosis-related lncRNA signatures to predict the prognosis and immune microenvironment of breast cancer patients

Long non‐coding RNA AC018926.2 regulates palmitic acid exposure‐compromised osteogenic potential of periodontal ligament stem cells via the ITGA2/FAK/AKT pathway

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