scholarly journals CircularLRRC7 is a Potential Tumor Suppressor Associated With miR-1281 and PDXP Expression in Glioblastoma

2021 ◽  
Vol 8 ◽  
Author(s):  
Xue Kong ◽  
Ruiting Xu ◽  
Wei Wang ◽  
Minghui Zeng ◽  
Yuan Li ◽  
...  

Circular RNAs (circRNAs) are usually enriched in neural tissues, yet about 80% circRNAs have lower expression in gliomas relative to normal brains, highlighting the importance of circRNAs as tumor suppressors. However, the clinical impact as well as the pathways regulated by the tumor-suppressive circRNAs remain largely unknown in glioblastoma (GBM). Through bioinformatic analysis followed by experimental validation, we found that hsa_circ_0114014 (circLRRC7) was dramatically down-regulated in GBM when compared with normal brain tissues (p < 0.0001). GBM patients with a lower circLRRC7 expression had poorer progression-free survival (PFS, p < 0.05) and overall survival (OS, p < 0.05). Analyses of the predicted target miRNAs of circLRRC7 in CSCD and CRI databases, in combination with the miRNA expression data in GBMs and normal brains from GSE database, revealed miR-1281 as a potential downstream target of circLRRC7. Subsequently, the target genes of hsa-mir-1281 were predicted by TargetScan, miRDB and miRNATAR databases. Intersection analysis and correlation test indicated that PDXP was a potential target of miR-1281. In summary, circLRRC7 may be a tumor suppressor that associated with miR-1281 and PDXP expression in GBM, which may provide novel therapeutic targets for GBM treatment.

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 921
Author(s):  
Aleksandra Lipka ◽  
Jan Pawel Jastrzebski ◽  
Lukasz Paukszto ◽  
Karol Gustaw Makowczenko ◽  
Elzbieta Lopienska-Biernat ◽  
...  

Impaired fetal growth is one of the most important causes of prematurity, stillbirth and infant mortality. The pathogenesis of idiopathic fetal growth restriction (FGR) is poorly understood but is thought to be multifactorial and comprise a range of genetic causes. This research aimed to investigate non-coding RNAs (lncRNAs) in the placentas of male and female fetuses affected by FGR. RNA-Seq data were analyzed to detect lncRNAs, their potential target genes and circular RNAs (circRNAs); a differential analysis was also performed. The multilevel bioinformatic analysis enabled the detection of 23,137 placental lncRNAs and 4263 of them were classified as novel. In FGR-affected female fetuses’ placentas (ff-FGR), among 19 transcriptionally active regions (TARs), five differentially expressed lncRNAs (DELs) and 12 differentially expressed protein-coding genes (DEGs) were identified. Within 232 differentially expressed TARs identified in male fetuses (mf-FGR), 33 encompassed novel and 176 known lncRNAs, and 52 DEGs were upregulated, while 180 revealed decreased expression. In ff-FGR ACTA2-AS1, lncRNA expression was significantly correlated with five DEGs, and in mf-FGR, 25 TARs were associated with DELs correlated with 157 unique DEGs. Backsplicing circRNA processes were detected in the range of H19 lncRNA, in both ff- and mf-FGR placentas. The performed global lncRNAs characteristics in terms of fetal sex showed dysregulation of DELs, DEGs and circRNAs that may affect fetus growth and pregnancy outcomes. In female placentas, DELs and DEGs were associated mainly with the vasculature, while in male placentas, disturbed expression predominantly affected immune processes.


2020 ◽  
Author(s):  
Timothée Zaragori ◽  
Merwan Ginet ◽  
Pierre-Yves Marie ◽  
Veronique Roch ◽  
Rachel Grignon ◽  
...  

Abstract Background: Static 18 F-FDopa PET images are currently used for identifying patients with glioma recurrence/progression after treatment, although the additional diagnostic value of dynamic parameters remains unknown in this setting. The aim of the present study was to evaluate the performances of static and dynamic 18 F-FDopa PET parameters for detecting patients with glioma recurrence/progression as well as to assess further relationships with patient outcome. Fifty-one consecutive patients who underwent an 18 F-FDopa PET for a suspected glioma recurrence/progression at post-resection MRI, were retrospectively included. Static parameters including mean and maximum tumor-to-normal-brain (TBR), tumor-to-striatum (TSR) ratios, and metabolic tumor volume (MTV), as well as dynamic parameters with time-to-peak (TTP) values and curve slope, were tested for predicting: 1) glioma recurrence/progression at 6-months after the PET exam and 2) survival on longer follow-up. Results: All static parameters were significant predictors of a glioma recurrence/progression (accuracy≥94%) with all parameters also associated with mean progression-free survival (PFS) in the overall population (all p<0.001, 29.7 vs. 0.4 months for TBR max , TSR max and MTV). The curve slope was the sole dynamic PET predictor of glioma recurrence/progression (accuracy=76.5%) and was also associated with the mean PFS (p<0.001, 18.0 vs. 0.4 months). However, no additional information was provided relative to static parameters in multivariate analysis. Conclusion: Although patients with glioma recurrence/progression can be detected by both static and dynamic 18 F-FDopa PET parameters, most of this diagnostic information can be achieved by conventional static parameters.


Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 2038
Author(s):  
Rada Amin ◽  
Kaushlendra Tripathi ◽  
Ralph D. Sanderson

Heparanase (HPSE) is an endoglycosidase that cleaves heparan sulfate and has been shown in various cancers to promote metastasis, angiogenesis, osteolysis, and chemoresistance. Although heparanase is thought to act predominantly extracellularly or within the cytoplasm, it is also present in the nucleus, where it may function in regulating gene transcription. Using myeloma cell lines, we report here that heparanase enhances chromatin accessibility and confirm a previous report that it also upregulates the acetylation of histones. Employing the Multiple Myeloma Research Foundation CoMMpass database, we demonstrate that patients expressing high levels of heparanase display elevated expression of proteins involved in chromatin remodeling and several oncogenic factors compared to patients expressing low levels of heparanase. These signatures were consistent with the known function of heparanase in driving tumor progression. Chromatin opening and downstream target genes were abrogated by inhibition of heparanase. Enhanced levels of heparanase in myeloma cells led to a dramatic increase in phosphorylation of PTEN, an event known to stabilize PTEN, leading to its inactivity and loss of tumor suppressor function. Collectively, this study demonstrates that heparanase promotes chromatin opening and transcriptional activity, some of which likely is through its impact on diminishing PTEN tumor suppressor activity.


1999 ◽  
Vol 880 (1 CELL AND MOLE) ◽  
pp. 31-37 ◽  
Author(s):  
PAUL J. CHIAO ◽  
KELLY K. HUNT ◽  
ANA M. GRAU ◽  
ARAM ABRAMIAN ◽  
JASON FLEMING ◽  
...  

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Yuan Zhang ◽  
Lei Yang ◽  
Jia Shi ◽  
Yunfei Lu ◽  
Xiaorong Chen ◽  
...  

Objective. This study is aimed at investigating the predictive value of CENPA in hepatocellular carcinoma (HCC) development. Methods. Using integrated bioinformatic analysis, we evaluated the CENPA mRNA expression in tumor and adjacent tissues and correlated it with HCC survival and clinicopathological features. A Cox regression hazard model was also performed. Results. CENPA mRNA was significantly upregulated in tumor tissues compared with that in adjacent tissues, which were validated in The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) series (all P<0.01). In the Kaplan-Meier plotter platform, the high level of CENPA mRNA was significantly correlated with overall survival (OS), disease-free survival (DFS), recurrence-free survival (RFS), and progression-free survival (PFS) in HCC patients (all log rank P<0.01). For validation in GSE14520 and pan-TCGA dataset, HCC patients with CNEPA mRNA overexpression had poor OS compared with those with low CENPA mRNA (log rank P=0.025 and P<0.0001, respectively), and those with high CENPA had poor DFS in TCGA (log rank P=0.0001). Additionally, CENPA mRNA were upregulated in HCC patients with alpha-fetoprotein (AFP) elevation, advanced TNM stage, larger tumor size, advanced AJCC stage, advanced pathology grade, and vascular invasion (all P<0.05). A Cox regression model including CENPA, OIP5, and AURKB could predict OS in HCC patients effectively (AUC=0.683). Conclusion. Overexpressed in tumors, CENPA might be an oncogenic factor in the development of HCC patients.


2021 ◽  
Vol 12 (2) ◽  
Author(s):  
Yongbin Chi ◽  
Wenlong Zheng ◽  
Guangyu Bao ◽  
Lifeng Wu ◽  
Xiaoxue He ◽  
...  

AbstractA growing number of circular RNAs (circRNAs) have been identified and verified in several cancers. However, highly efficient therapeutic methods based on circRNAs in lung cancer remain largely unexplored. In the present study, we identified a novel circular RNA, hsa_circ_103820, based on Gene Expression Omnibus (GEO) data. Functionally, overexpression of hsa_circ_103820 showed significant inhibitory effects on the proliferation, migration and invasion of lung cancer cells, and knockdown of hsa_circ_103820 played promoting roles. Regarding the mechanism, we revealed that miR-200b-3p was a direct target of hsa_circ_103820 and that LATS2 and SOCS6 were the downstream target genes of miR-200b-3p. Therefore, we identified a novel potential tumor suppressive function of hsa_circ_103820 in lung cancer.


2000 ◽  
Vol 14 (11) ◽  
pp. 1319-1331 ◽  
Author(s):  
Frank T. Kolligs ◽  
Barbara Kolligs ◽  
Karen M. Hajra ◽  
Gang Hu ◽  
Masachika Tani ◽  
...  

β-Catenin and γ-catenin (plakoglobin), vertebrate homologs of Drosophila armadillo, function in cell adhesion and the Wnt signaling pathway. In colon and other cancers, mutations in the APC tumor suppressor protein orβ-catenin's amino terminus stabilizeβ-catenin, enhancing its ability to activate transcription of Tcf/Lef target genes. Thoughβ- and γ-catenin have analogous structures and functions and like binding to APC, evidence that γ-catenin has an important role in cancer has been lacking. We report here that APC regulates bothβ- and γ-catenin andγ-catenin functions as an oncogene. In contrast to β-catenin, for which only amino-terminal mutated forms transform RK3E epithelial cells, wild-type and several amino-terminal mutated forms of γ-catenin had similar transforming activity. γ-Catenin's transforming activity, like β-catenin's, was dependent on Tcf/Lef function. However, in contrast toβ-catenin, γ-catenin strongly activated c-Myc expression and c-Myc function was crucial for γ-catenin transformation. Our findings suggest APC mutations alter regulation of bothβ- and γ-catenin, perhaps explaining why the frequency of APC mutations in colon cancer far exceeds that of β-catenin mutations. Elevated c-Myc expression in cancers with APC defects may be due to altered regulation of both β- andγ-catenin. Furthermore, the data implyβ- and γ-catenin may have distinct roles in Wnt signaling and cancer via differential effects on downstream target genes.


2020 ◽  
Author(s):  
Jiancheng Lu ◽  
Zijian Zhou ◽  
Jingzi Wang ◽  
Xiao Yang ◽  
Hao Yu ◽  
...  

Abstract Background: Circular RNAs (circRNAs) are noncoding RNAs that have the structure of a covalently closed loop. Increasing data has proved that circRNA can influence the development and progression of tumors. CircFAM114A2 is generated from several exons of FAM114A2. However, the function and mechanisms of circFAM114A2 in bladder cancer (BCa) remain unclear. Methods: Here, to elucidate the potential roles of circFAM114A2 in BCa, we conducted RNA-sequencing on 5 pairs of BCa samples and screened for circRNAs. CircRNAs, microRNAs (miRNAs) and mRNAs, as well as levels of P27 and P21, in human cells and tissues were detected by qRT-PCR and western blot, respectively. CircRNA-miRNA interactions and miRNA-downstream mRNAs interactions were investigated by RNA pull-down assay and fluorescence in situ hybridization (FISH) or luciferase reporter assays, respectively. Then, the function of circFAM114A2 in BCa was explored using cell proliferation, cell cycle and tumorigenesis assays in nude mice. Finally, the function of circFAM114A2 in cisplatin chemo-sensitivity in BCa was detected by IC50 and tumor formation of xenograft in cisplatin-treated nude mice. Results: We discovered that circFAM114A2 levels were decreased in BCa cell lines and tissues. According to follow-up data, BCa patients with higher circFAM114A2 expression had better survival. Importantly, the levels of circFAM114A2 were associated with the histological grade of BCa. Overexpression of circFAM114A2 inhibited cell proliferation and increased sensitivity to cisplatin chemotherapy. Mechanistically, circFAM114A2 directly sponged miR-222-3p/miR-146a-5p and subsequently influenced the expression of the downstream target genes P27/P21, which, in turn, inhibited progression of BCa. Conclusion: In conclusion, circFAM114A2 acted as a tumor suppressor through a novel circFAM114A2/miR-222-3p/P27 and circFAM114A2/miR-146a-5p/P21 pathway. CircFAM1142 has therefore great potential as a prognostic biomarker and therapeutic target for BCa.


Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2622 ◽  
Author(s):  
Tae-Su Han ◽  
Keun Hur ◽  
Hyun-Soo Cho ◽  
Hyun Seung Ban

The three major members of non-coding RNAs (ncRNAs), named microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), play an important role in hepatocellular carcinoma (HCC) development. Recently, the competing endogenous RNA (ceRNA) regulation model described lncRNA/circRNA as a sponge for miRNAs to indirectly regulate miRNA downstream target genes. Accumulating evidence has indicated that ceRNA regulatory networks are associated with biological processes in HCC, including cancer cell growth, epithelial to mesenchymal transition (EMT), metastasis, and chemoresistance. In this review, we summarize recent discoveries, which are specific ceRNA regulatory networks (lncRNA/circRNA-miRNA-mRNA) in HCC and discuss their clinical significance.


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