Identification of clinical trait–related lncRNA and mRNA biomarkers with weighted gene co-expression network analysis as useful tool for personalized medicine in ovarian cancer

Li, Na; Zhan, Xianquan

doi:10.1007/s13167-019-00175-0

Cited by 109 publications

(91 citation statements)

References 39 publications

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“…Therefore, the repression of HOTAIRM1 may affect miRNAs other than miR-107. A previous study to identify prognosis-related lncRNAs in ovarian cancer tissues, showed that HOTAIRM1 regulates hub genes through several miRNAs, including miR-107, miR-103a-3p, miR-129-5p, miR-152-3p, miR-148a-3p, and miR-148b-3p 32 . In vitro and in vivo studies demonstrated that HOTAIRM1 may play a negative role in the development of head and neck tumors through the HOTAIRM1/microRNA-148a axis 9 .…”

Section: Discussionmentioning

confidence: 99%

RETRACTED ARTICLE: The HOTAIRM1/miR-107/TDG axis regulates papillary thyroid cancer cell proliferation and invasion

Chai

et al. 2020

Cell Death Dis

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The long noncoding RNA (lncRNA), HOX antisense intergenic RNA myeloid 1 (HOTAIRM1), has been shown to act as a tumor suppressor in various human cancers. However, the overall biological roles and clinical significance of HOTAIRM1 in papillary thyroid cancer (PTC) have not been investigated. In this study, we used quantitative reverse transcription PCR (qRT-PCR) to show that HOTAIRM1 was significantly downregulated in PTC tissues and low HOTAIRM1 expression levels were associated with lymph node metastasis and advanced TNM stage. We performed Cell Counting Kit-8, plate colony-formation, flow cytometric apoptosis, transwell, and scratch wound healing assays. Overexpression of HOTAIRM1 was found to inhibit PTC cell proliferation, invasion, and migration in vitro. Additionally, we identified miR-107 as a target of HOTAIRM1 using online bioinformatics tools. Dual-luciferase reporter gene and RNA immunoprecipitation assays were used to confirm that HOTAIRM1 acted as a competing endogenous RNA of miR-107. Furthermore, enhancement of miR-107 could potentially reverse the effects of HOTAIRM1 overexpression in vitro. Inhibition of miR-107 suppressed PTC cell proliferation, invasion, and migration in vitro. HOTAIRM1 overexpression and miR-107 inhibition impaired tumorigenesis in vivo in mouse xenografts. Bioinformatics prediction and a dual-luciferase reporter gene assay demonstrated the binding between miR-107 and the 3′-untranslated region of TDG. The results of qRT-PCR and western blotting assays suggested that HOTAIRM1 could regulate the expression of TDG in an miR-107meditated manner. In conclusion, we validated HOTAIRM1 as a novel tumor-suppressor lncRNA in PTC and proposed that the HOTAIRM1/miR-107/TDG axis may serve as a therapeutic target for PTC.

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Section: Discussionmentioning

confidence: 99%

RETRACTED ARTICLE: The HOTAIRM1/miR-107/TDG axis regulates papillary thyroid cancer cell proliferation and invasion

Chai

et al. 2020

Cell Death Dis

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“…The diagnosis of OCs based on those common biomarkers is still unsatisfactory. To accelerates predictive, preventive, and personalized medicine (PPPM) practice allowing prediction of response with substantially increased accuracy, various omics technologies, including transcriptome and proteome, have been tried [47][48][49].…”

Section: Limitations Clinical Meaning and Future Directionmentioning

confidence: 99%

Calcium Channels as Novel Therapeutic Targets for Ovarian Cancer Stem Cells

Lee

Kim

et al. 2020

IJMS

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Drug resistance in epithelial ovarian cancer (EOC) is reportedly attributed to the existence of cancer stem cells (CSC), because in most cancers, CSCs still remain after chemotherapy. To overcome this limitation, novel therapeutic strategies are required to prevent cancer recurrence and chemotherapy-resistant cancers by targeting cancer stem cells (CSCs). We screened an FDA-approved compound library and found four voltage-gated calcium channel blockers (manidipine, lacidipine, benidipine, and lomerizine) that target ovarian CSCs. Four calcium channel blockers (CCBs) decreased sphere formation, viability, and proliferation, and induced apoptosis in ovarian CSCs. CCBs destroyed stemness and inhibited the AKT and ERK signaling pathway in ovarian CSCs. Among calcium channel subunit genes, three L- and T-type calcium channel genes were overexpressed in ovarian CSCs, and downregulation of calcium channel genes reduced the stem-cell-like properties of ovarian CSCs. Expressions of these three genes are negatively correlated with the survival rate of patient groups. In combination therapy with cisplatin, synergistic effect was shown in inhibiting the viability and proliferation of ovarian CSCs. Moreover, combinatorial usage of manidipine and paclitaxel showed enhanced effect in ovarian CSCs xenograft mouse models. Our results suggested that four CCBs may be potential therapeutic drugs for preventing ovarian cancer recurrence.

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“…OTUD6B-AS1 is transcribed from the opposite strand of the OTUD6B gene, which is located on chromosome 8 in head-to-head orientation to OTUD6BAS1 [26]. It was reported that high OTUD6B-AS1 expression indicates poor prognosis in ovarian cancer [27]. However, Gang Wang et al [28] found that high OTUD6B-AS1 expression was associated with improved survival and inhibited clear cell renal cell carcinoma proliferation via the Wnt/β-catenin signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

Immune-related lncRNAs as predictors of survival in breast cancer: a prognostic signature

Zhao

et al. 2020

Preprint

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Background: Breast cancer is a highly heterogeneous disease, this poses challenges for classification and management. Long non-coding RNAs play acrucial role in the breast cancersdevelopment and progression, especially in tumor-related immune processes which have become the most rapidly investigated area. Therefore, we aimed at developing an immune-related lncRNA signature to improve the prognosis prediction of breast cancer.Methods: We obtained breast cancer patient samples and corresponding clinical data from The Cancer Genome Atlas (TCGA) database. Immune-related lncRNAs were screened by co-expression analysis of immune-related genes which were downloaded from the Immunology Database and Analysis Portal (ImmPort). Clinical patient samples were randomly separated into training and testing sets. In the training set, univariate Cox regression analysis and LASSO regression were utilized to build a prognostic immune-related lncRNA signature. The signature was validated in the training set, testing set, and whole cohorts by the Kaplan–Meier log-rank test, time-dependent ROC curve analysis, principal component analysis, univariate andmultivariate Cox regression analyses.Results:A total of 937 immune- related lncRNAs were identified, 15 candidate immune-related lncRNAs were significantly associated with overall survival (OS). Eight of these lncRNAs (OTUD6B-AS1, AL122010.1, AC136475.2, AL161646.1, AC245297.3, LINC00578, LINC01871, AP000442.2) were selected for establishment of the risk prediction model. The OS of patients in the low-risk group was higher than that of patients in the high-risk group(p=1.215e−06 in the training set; p=0.0069 in the validation set; p=1.233e−07 in whole cohort). The time-dependent ROC curve analysis revealed that the AUCs for OS in the first, eighth, and tenth year were 0.812, 0.81, and 0.857, respectively, in the training set,0.615, 0.68, 0.655 in the validation set, and 0.725, 0.742, 0.741 in the total cohort. Multivariate Cox regression analysis indicated the model was a reliable and independent indicator for the prognosis of breast cancer in the training set (HR= 1.432; 95% CI 1.204−1.702, p<0.001), validation set (HR= 1.162; 95% CI 1.004−1.345, p = 0.044), and whole set (HR=1.240; 95% CI 1.128−1.362, p<0.001). GSEA analysis revealed a strong connection between the signature and immune-related biological processes and pathways.Conclusions:We constructed and verified a robust signature of 8 immune-related lncRNAs for the prediction of breast cancer patient survival.

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Identification of clinical trait–related lncRNA and mRNA biomarkers with weighted gene co-expression network analysis as useful tool for personalized medicine in ovarian cancer

Cited by 109 publications

References 39 publications

RETRACTED ARTICLE: The HOTAIRM1/miR-107/TDG axis regulates papillary thyroid cancer cell proliferation and invasion

RETRACTED ARTICLE: The HOTAIRM1/miR-107/TDG axis regulates papillary thyroid cancer cell proliferation and invasion

Calcium Channels as Novel Therapeutic Targets for Ovarian Cancer Stem Cells

Immune-related lncRNAs as predictors of survival in breast cancer: a prognostic signature

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