Discovery of 5-Signature Predicting Survival of Patients with Lower-Grade Glioma

Xiao, Huaming; Bai, Jianan; Yan, Mingbu; Ji, Kai; Tian, Wei; Liu, Dagang; Ning, Tongbo; Liu, Xiaoyun; Zou, Jidian

doi:10.1016/j.wneu.2019.02.147

Cited by 6 publications

(5 citation statements)

References 27 publications

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“…Concerning miRNAs involved in glioblastoma, miR-15b-5p has been found up-regulated in aggressive gliomas and its expression correlates with poor prognosis for glioblastoma [26][27][28]. This observation confirmed a previous study published by Xiao et al [29] who found, after univariate and multivariate Cox regression analysis, two miRNAs (hsa-miR-10b-5p and hsa-miR-15b-5p) that were predictive of high-risk for poor prognosis in glioblastoma patients [29,30]. The involvement of miR-15b-5p in other types of cancers has been also reported [31][32][33][34].…”

Section: Introductionsupporting

confidence: 88%

Treatment of Human Glioblastoma U251 Cells with Sulforaphane and a Peptide Nucleic Acid (PNA) Targeting miR-15b-5p: Synergistic Effects on Induction of Apoptosis

et al. 2022

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Glioblastoma multiforme (GBM) is a lethal malignant tumor accounting for 42% of the tumors of the central nervous system, the median survival being 15 months. At present, no curative treatment is available for GBM and new drugs and therapeutic protocols are urgently needed. In this context, combined therapy appears to be a very interesting approach. The isothiocyanate sulforaphane (SFN) has been previously shown to induce apoptosis and inhibit the growth and invasion of GBM cells. On the other hand, the microRNA miR-15b is involved in invasiveness and proliferation in GBM and its inhibition is associated with the induction of apoptosis. On the basis of these observations, the objective of the present study was to determine whether a combined treatment using SFN and a peptide nucleic acid interfering with miR-15b-5p (PNA-a15b) might be proposed for increasing the pro-apoptotic effects of the single agents. To verify this hypothesis, we have treated GMB U251 cells with SFN alone, PNA-a15b alone or their combination. The cell viability, apoptosis and combination index were, respectively, analyzed by calcein staining, annexin-V and caspase-3/7 assays, and RT-qPCR for genes involved in apoptosis. The efficacy of the PNA-a15b determined the miR-15b-5p content analyzed by RT-qPCR. The results obtained indicate that SFN and PNA-a15b synergistically act in inducing the apoptosis of U251 cells. Therefore, the PNA-a15b might be proposed in a “combo-therapy” associated with SFN. Overall, this study suggests the feasibility of using combined treatments based on PNAs targeting miRNA involved in GBM and nutraceuticals able to stimulate apoptosis.

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Section: Introductionsupporting

confidence: 88%

Treatment of Human Glioblastoma U251 Cells with Sulforaphane and a Peptide Nucleic Acid (PNA) Targeting miR-15b-5p: Synergistic Effects on Induction of Apoptosis

et al. 2022

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“…In addition, 5 miRNAs, including hsa-miR-15a-5p, hsa-miR-16-5p, hsa-miR-15b-5p, hsa-miR-34c-5p and hsa-miR-424-5p, had pro-tumorigenic effects and were correlated with poor prognosis in LGG. Higher expression of hsa-miR-15b-5p has been reported to be associated with a short survival time of patients with LGG (36). Has-miR-15a-5p promotes the proliferation and invasion of colorectal cancer by targeting CCND1 (37).…”

Section: Discussionmentioning

confidence: 99%

Decreased SPTBN2 expression regulated by the ceRNA network is associated with poor prognosis and immune infiltration in low‑grade glioma

et al. 2023

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The majority of low-grade gliomas (LGGs) in adults invariably progress to glioblastoma over time. Spectrin β non-erythrocytic 2 (SPTBN2) is detected in numerous tumors and is involved in tumor occurrence and metastasis. However, the specific roles and detailed mechanisms of SPTBN2 in LGG are largely unknown. The present study performed pan-cancer analysis for the expression and prognosis of SPTBN2 in LGG using The Cancer Genome Atlas and The Genotype-Tissue Expression. Western blotting was used to detect the amount of SPTBN2 between glioma tissues and normal brain tissues. Subsequently, based on expression, prognosis, correlation and immune infiltration, non-coding RNAs (ncRNAs) were identified that regulated SPTBN2 expression. Finally, tumor immune infiltrates associated with SPTBN2 and prognosis were performed. Lower expression of SPTBN2 was correlated with an unfavorable outcome in LGG. A significant correlation between the low SPTBN2 mRNA expression and poor clinicopathological features was observed, including wild-type isocitrate dehydrogenase status (P<0.001), 1p/19q non-codeletion (P<0.001) and elders (P=0.019). The western blotting results revealed that, compared with normal brain tissues, the amount of SPTBN2 was significantly lower in LGG tissues (P=0.0266). Higher expression of five microRNAs (miRs/miRNAs), including hsa-miR-15a-5p, hsa-miR-15b-5p, hsa-miR-16-5p, hsa-miR-34c-5p and hsa-miR-424-5p, correlated with poor prognosis by targeting SPTBN2 in LGG. Subsequently, four long ncRNAs (lncRNAs) [ARMCX5-GPRASP2, BASP1-antisense RNA 1 (AS1), EPB41L4A-AS1 and LINC00641] were observed in the regulation of SPTBN2 via five miRNAs. Moreover, the expression of SPTBN2 was significantly correlated with tumor immune infiltration, immune checkpoint expression and biomarkers of immune cells. In conclusion, SPTBN2 was lowly expressed and correlated with an unfavorable prognosis in LGG. A total of six miRNAs and four lncRNAs were identified as being able to modulate SPTBN2 in a lncRNA-miRNA-mRNA network of LGG. Furthermore, the current findings also indicated that SPTBN2 possessed anti-tumor roles by regulating tumor immune infiltration and immune checkpoint expression.

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“…Similarly, elevated pre-miR-10b expression in prostate cancer has previously been associated with poor recurrence-free survival 19 . Elevated miR-10b-5p expression has also been associated with shorter survival in glioma 20 and non-small-cell lung cancer 21 , whereas miR-10b-5p has been reported as downregulated in breast and renal cancer 22,23 . In seeming contrast to our findings, two previous studies reported that miR-23a-3p was downregulated in prostate cancer vs. normal tissue 24,25 .…”

Section: Discussionmentioning

confidence: 99%

Validation of the four-miRNA biomarker panel MiCaP for prediction of long-term prostate cancer outcome

Strand

Schmidt

Weiss

et al. 2020

Sci Rep

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Improved prostate cancer prognostic biomarkers are urgently needed. We previously identified the four-miRnA prognostic biomarker panel MiCaP ((miR-23a-3p × miR-10b-5p)/(miR-133a-3p × miR-374b-5p)) for prediction of biochemical recurrence (BCR) after radical prostatectomy (RP). Here, we identified an optimal numerical cutoff for MiCaP dichotomisation using a training cohort of 475 RP patients and tested this in an independent cohort of 281 RP patients (PCA281). Kaplan-Meier, uni-and multivariate Cox regression analyses were conducted for multiple endpoints: BCR, metastatic-(mPC) and castration-resistant prostate cancer (CRPC), prostate cancer-specific (PCSS) and overall survival (OS). Functional effects of the four MiCaP miRNAs were assessed by overexpression and inhibition experiments in prostate cancer cell lines. We found the numerical value 5.709 optimal for MiCaP dichotomisation. This was independently validated in PCA281, where a high MiCaP score significantly [and independent of the Cancer of the Prostate Risk Assessment Postsurgical (CAPRA-S) score] predicted BCR, progression to mPC and CRPC, and PCSS, but not OS. Harrell's C-index increased upon addition of MiCaP to CAPRA-S for all endpoints. Inhibition of miR-23a-3p and miR-10b-5p, and overexpression of miR-133a-3p and miR-374b-5p significantly reduced cell survival. Our results may promote future implementation of a MiCaP-based test for improved prostate cancer risk stratification. Prostate cancer is a significant healthcare problem, globally causing > 300,000 deaths/year 1. While many prostate cancers are indolent, a subset progress to metastatic (mPC) and castration-resistant (CRPC) disease, causing significant morbidity and mortality. Routine prognostic tools for early-stage prostate cancer are suboptimal, causing overtreatment of indolent prostate cancer and undertreatment of aggressive prostate cancer 2. Thus, novel prognostic biomarkers are urgently needed to improve risk stratification and guide individualised treatment. MicroRNAs (miRNAs) are small noncoding RNAs that bind complementary sequences in target messenger RNAs (mRNAs), inhibiting mRNA translation and stability 3. miRNAs regulate genes involved in key cellular processes, including differentiation, cell-cycle control, and migration. Furthermore, dysregulation of miRNA expression is a hallmark of cancer development and progression 3,4 , and miRNAs have shown promising prognostic biomarker potential in prostate cancer 5-9. We recently identified the four-miRNA prognostic model MiCaP ((miR-23a-3p × miR-10b-5p)/(miR-133a-3p × miR-374b-5p)) 9 as an independent predictor of biochemical recurrence (BCR) in radical prostatectomy (RP) patients 9. Here, to promote future clinical implementation of a MiCaP test, we identified an optimal numerical cutoff value for MiCaP dichotomisation using a merged training cohort of 475 RP patients (PCA475)

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Discovery of 5-Signature Predicting Survival of Patients with Lower-Grade Glioma

Cited by 6 publications

References 27 publications

Treatment of Human Glioblastoma U251 Cells with Sulforaphane and a Peptide Nucleic Acid (PNA) Targeting miR-15b-5p: Synergistic Effects on Induction of Apoptosis

Treatment of Human Glioblastoma U251 Cells with Sulforaphane and a Peptide Nucleic Acid (PNA) Targeting miR-15b-5p: Synergistic Effects on Induction of Apoptosis

Decreased SPTBN2 expression regulated by the ceRNA network is associated with poor prognosis and immune infiltration in low‑grade glioma

Validation of the four-miRNA biomarker panel MiCaP for prediction of long-term prostate cancer outcome

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