In recent years, circular RNAs have been shown to serve as essential regulators in several human cancers. Nevertheless, the function and mechanism of CircRNA in cervical cancer remain elusive. In the ...present study, we showed that hsa_circRNA_101996 was highly expressed in cervical cancer tissues compared with matched normal tissues by bioinformatics analysis. We showed that the expression level of hsa_circRNA_101996 in cervical cancer tissues was positively correlated with TNM stage, tumor size, and lymph node metastasis. Moreover, higher levels of hsa_circRNA_101996 were related to poor outcomes of cervical cancer patients. We found that knockdown of hsa_circRNA_101996 significantly inhibited the proliferation, cell cycle, migration, and invasion of cervical cancer cells. Mechanistically, we demonstrated that hsa_circRNA_101996 served as a sponge of miR‐8075, which targeted TPX2 in cervical cancer cells. We showed that miR‐8075 that was downregulated in cervical cancer tissues repressed cervical cancer cell proliferation, migration, and invasion. Furthermore, we validated that upregulation of TPX2 by hsa_circRNA_101996‐mediated inhibition of miR‐8075 contributed to cervical cancer proliferation, migration, and invasion. Taken together, our findings revealed a novel mechanism that hsa_circRNA_101996‐miR‐8075‐TPX2 network promoted cervical cancer progression.
CircRNA hsa_circRNA_101996 increases cervical cancer proliferation and invasion through activating TPX2 expression by restraining miR‐8075.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Alteration of tissue mechanical properties is a physical hallmark of solid tumors including gliomas. How tumor cells sense and regulate tissue mechanics is largely unknown. Here, we show that ...mechanosensitive ion channel Piezo regulates mitosis and tissue stiffness of Drosophila gliomas, but not non-transformed brains. PIEZO1 is overexpressed in aggressive human gliomas and its expression inversely correlates with patient survival. Deleting PIEZO1 suppresses the growth of glioblastoma stem cells, inhibits tumor development, and prolongs mouse survival. Focal mechanical force activates prominent PIEZO1-dependent currents from glioma cell processes, but not soma. PIEZO1 localizes at focal adhesions to activate integrin-FAK signaling, regulate extracellular matrix, and reinforce tissue stiffening. In turn, a stiffer mechanical microenvironment elevates PIEZO1 expression to promote glioma aggression. Therefore, glioma cells are mechanosensory in a PIEZO1-dependent manner, and targeting PIEZO1 represents a strategy to break the reciprocal, disease-aggravating feedforward circuit between tumor cell mechanotransduction and the aberrant tissue mechanics.
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•Drosophila Piezo regulates cell proliferation and tissue stiffening of gliomas•Human PIEZO1 is overexpressed in aggressive gliomas and predicts poor survival•Piezo/PIEZO1 interacts with integrin-FAK signaling to regulate tumor stiffness•PIEZO1 co-opts aberrant tissue mechanics to promote glioma aggression
PIEZO1 is an ion channel that converts mechanical stimuli into cellular signaling. Here, Chen et al. perform multi-species studies to define a feedforward circuit mediated by PIEZO1 and tumor tissue mechanics to promote glioma growth.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background Solid components of part-solid nodules (PSNs) at CT are reflective of invasive adenocarcinoma, but studies describing radiomic features of PSNs and the perinodular region are lacking. ...Purpose To develop and to validate radiomic signatures diagnosing invasive lung adenocarcinoma in PSNs compared with the Brock, clinical-semantic features, and volumetric models. Materials and Methods This retrospective multicenter study (
, NCT03872362) included 291 patients (median age, 60 years; interquartile range, 55-65 years; 191 women) from January 2013 to October 2017 with 297 PSN lung adenocarcinomas split into training (
= 229) and test (
= 68) data sets. Radiomic features were extracted from the different regions (gross tumor volume GTV, solid, ground-glass, and perinodular). Random-forest models were trained using clinical-semantic, volumetric, and radiomic features, and an online nodule calculator was used to compute the Brock model. Performances of models were evaluated using standard metrics such as area under the curve (AUC), accuracy, and calibration. The integrated discrimination improvement was applied to assess model performance changes after the addition of perinodular features. Results The radiomics model based on ground-glass and solid features yielded an AUC of 0.98 (95% confidence interval CI: 0.96, 1.00) on the test data set, which was significantly higher than the Brock (AUC, 0.83 95% CI: 0.72, 0.94;
= .007), clinical-semantic (AUC, 0.90 95% CI: 0.83, 0.98;
= .03), volumetric GTV (AUC, 0.87 95% CI: 0.78, 0.96;
= .008), and radiomics GTV (AUC, 0.88 95% CI: 0.80, 0.96;
= .01) models. It also achieved the best accuracy (93% 95% CI: 84%, 98%). Both this model and the model with added perinodular features showed good calibration, whereas adding perinodular features did not improve the performance (integrated discrimination improvement, -0.02;
= .56). Conclusion Separating ground-glass and solid CT radiomic features of part-solid nodules was useful in diagnosing the invasiveness of lung adenocarcinoma, yielding a better predictive performance than the Brock, clinical-semantic, volumetric, and radiomics gross tumor volume models.
See also the editorial by Nishino in this issue. Published under a CC BY 4.0 license.
The risk of cancer and associated mortality increases substantially in humans from the age of 65 years onwards
. Nonetheless, our understanding of the complex relationship between age and cancer is ...still in its infancy
. For decades, this link has largely been attributed to increased exposure time to mutagens in older individuals. However, this view does not account for the established role of diet, exercise and small molecules that target the pace of metabolic ageing
. Here we show that metabolic alterations that occur with age can produce a systemic environment that favours the progression and aggressiveness of tumours. Specifically, we show that methylmalonic acid (MMA), a by-product of propionate metabolism, is upregulated in the serum of older people and functions as a mediator of tumour progression. We traced this to the ability of MMA to induce SOX4 expression and consequently to elicit transcriptional reprogramming that can endow cancer cells with aggressive properties. Thus, the accumulation of MMA represents a link between ageing and cancer progression, suggesting that MMA is a promising therapeutic target for advanced carcinomas.
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FZAB, GEOZS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The long, noncoding RNA (lncRNA)
is an important epigenetic regulator with a critical role in human tumors. Here, we aimed to investigate the clinical application and the potential molecular ...mechanisms of
in gastric cancer tumorigenesis and progression.
The expression level of
was determined by RT-qPCR analysis in 190 pairs of gastric cancer tissues and adjacent normal gastric mucosa tissues (ANT). The biologic functions of
were assessed by
and
functional experiments. RNA protein pull-down assays and LS/MS mass spectrometry analysis were performed to detect and identify the
interacting protein FOXM1. Protein-RNA immunoprecipitation assays were conducted to examine the interaction of FOXM1 and
Chromatin immunoprecipitation (ChIP) and luciferase analyses were utilized to identify the binding site of FOXM1 on the
promoter.
The lncRNA
was significantly upregulated in gastric cancer tissues compared with ANTs. High expression of
predicted poor prognosis in patients with gastric cancer.
enhanced gastric cancer cell proliferation and invasion
and
directly bound FOXM1 protein and increased FOXM1 posttranslationally. Moreover,
is also a FOXM1-responsive lncRNA, and FOXM1 directly binds to the
promoter to activate its transcription. Finally,
fulfilled its oncogenic functions in a FOXM1-mediated manner.
Our study suggests that
promotes tumor progression by interacting with FOXM1.
may be a valuable prognostic predictor for gastric cancer, and the positive feedback loop of
-FOXM1 could be a therapeutic target in pharmacologic strategies.
.
The epithelial–mesenchymal transition (EMT) is a developmental program that enables stationary epithelial cells to gain the ability to migrate and invade as single cells. Tumor cells reactivate EMT ...to acquire molecular alterations that enable the partial loss of epithelial features and partial gain of a mesenchymal phenotype. Our understanding of the contribution of EMT to tumor invasion, migration, and metastatic outgrowth has evolved over the past decade. In this review, we provide a summary of both historic and recent studies on the role of EMT in the metastatic cascade from various experimental systems, including cancer cell lines, genetic mouse tumor models, and clinical human breast cancer tissues.
The epithelial–mesenchymal transition (EMT) enables primary epithelial tumor cells to acquire the ability to migrate and disseminate into the surrounding stroma and vasculature. A small proportion of circulating tumor cells and cell clusters eventually extravasate into distant organs. The reverse process, the mesenchymal–epithelial transition, allows proliferation and formation of macrometastases. The accompanying model summarizes our current understanding of the role of EMT in the metastatic cascade.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The purpose of this article is to determine the accuracy of CT in the detection of tumor invasion beyond the bowel wall and nodal involvement of colon carcinomas. A literature search was performed to ...identify studies describing the accuracy of CT in the staging of colon carcinomas. Studies including rectal carcinomas that were inseparable from colon carcinomas were excluded. Publication bias was explored by using a Deeks funnel plot asymmetry test. A hierarchic summary ROC model was used to construct a summary ROC curve and to calculate summary estimates of sensitivity, specificity, and diagnostic odds ratios (ORs).
On the basis of a total of 13 studies, pooled sensitivity, specificity, and diagnostic ORs for detection of tumor invasion beyond the bowel wall (T3-T4) were 90% (95% CI, 83-95%), 69% (95% CI, 62-75%), and 20.6 (95% CI, 10.2-41.5), respectively. For detection of tumor invasion depth of 5 mm or greater (T3cd-T4), estimates from four studies were 77% (95% CI, 66-85%), 70% (95% CI, 53-83%), and 7.8 (95% CI, 4.2-14.2), respectively. For nodal involvement (N+), 16 studies were included with values of 71% (95% CI, 59-81%), 67% (95% CI, 46-83%), and 4.8 (95% CI, 2.5-9.4), respectively. Two studies using CT colonography were included with sensitivity and specificity of 97% (95% CI, 90-99%) and 81% (95% CI, 65-91%), respectively, for detecting T3-T4 tumors. CT has good sensitivity for the detection of T3-T4 tumors, and evidence suggests that CT colonography increases its accuracy. Discriminating between T1-T3ab and T3cd-T4 cancer is challenging, but data were limited. CT has a low accuracy in detecting nodal involvement.
The efficacy of prospective cancer treatments is routinely estimated by in vitro cell-line proliferation screens. However, it is unclear whether tumor aggressiveness and patient survival are ...influenced more by the proliferative or the migratory properties of cancer cells. To address this question, we experimentally measured proliferation and migration phenotypes across more than 40 breast cancer cell-lines. Based on the latter, we built and validated individual predictors of breast cancer proliferation and migration levels from the cells' transcriptomics. We then apply these predictors to estimate the proliferation and migration levels of more than 1000 TCGA breast cancer tumors. Reassuringly, both estimates increase with tumor's aggressiveness, as qualified by its stage, grade, and subtype. However, predicted tumor migration levels are significantly more strongly associated with patient survival than the proliferation levels. We confirmed these findings by conducting siRNA knock-down experiments on the highly migratory MDA-MB-231 cell lines and deriving gene knock-down based proliferation and migration signatures. We show that cytoskeletal drugs might be more beneficial in patients with high predicted migration levels. Taken together, these results testify to the importance of migration levels in determining patient survival.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Yes-associated protein 1 (YAP1) exerts significant effects in various malignancies. However, the oncogenic role of YAP1 remains controversial, and the mechanism by which YAP1 regulates non-coding ...RNAs is still largely unknown. The present study aimed to assess the effect of YAP1 on the malignant behaviors of colorectal carcinoma (CRC) and explore the underlying regulatory mechanism of the YAP1-MALAT1-miR-126-5p axis. YAP1 was highly expressed in CRC tissues as assessed by GSE20916 and its expression was negatively correlated with overall survival in 83 CRC cases. Meanwhile, YAP1 promoted proliferation, invasion, and migration in colon cancer cells, in vitro and in vivo. MALAT1 was obviously expressed, with differential expression of 11 lncRNAs in HCT116 cells after transfection with siYAP1 or si-Ctl. Based on bioinformatics prediction, immunoprecipitation (IP), and chromatin immunoprecipitation (ChIP), the interaction of YAP1 with TCF4/β-catenin was regulated by MALAT1. Bioinformatics prediction, dual luciferase assay, RNA-IP, and RNA pull-down assay demonstrated that YAP1-induced MALAT1 promoted the expression of metastasis-associated molecules such as VEGFA, SLUG, and TWIST, by sponging miR-126-5p in CRC. These findings indicated that the YAP1-MALAT1-miR-126-5p axis could control angiogenesis and epithelial-mesenchymal transition in CRC, providing potential biomarkers and therapeutic targets for CRC.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The movement of cancer cells into tissue surrounding the tumour and the vasculature is the first step in the spread of metastatic cancers. Recent advances in imaging, the use of 3D model systems and ...the application of microarray technologies have yielded new insights into these processes. This work has challenged our views about what causes cancer cells to become motile in the first place, and has demonstrated that cancer cells can move in many different ways.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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