p120 RasGAP and ZO-2 are essential for Hippo signaling and tumor suppressor function mediated by p190A RhoGAP.

ARHGAP35 , which encodes p190A RhoGAP (p190A), is a major cancer gene. p190A is a tumor suppressor that activates the Hippo pathway. p190A was originally cloned via direct binding to p120 RasGAP (RasGAP). Here, we determine that a novel interaction of p190A with the tight junction-associated protein ZO-2 is dependent on RasGAP. We establish that both RasGAP and ZO-2 are necessary for p190A to activate LATS kinases, elicit mesenchymal-to-epithelial transition, promote contact inhibition of cell proliferation and suppress tumorigenesis. Moreover, RasGAP and ZO-2 are required for transcriptional modulation by p190A. Finally, we demonstrate that low ARHGAP35 expression is associated with shorter survival in patients with high, but not low, transcript levels of TJP2 encoding ZO-2. Hence, we define a tumor suppressor interactome of p190A that includes ZO-2, an established constituent of the Hippo pathway, and RasGAP, which despite strong association with Ras signaling, is essential for p190A to activate LATS kinases.

Iron metabolism in colorectal cancer.

Iron, as one of the essential trace elements in the human body, is involved in a wide range of critical biochemical reactions and physiological processes, including the maintenance of the normal cell cycle, mitochondrial function, nucleotide metabolism, and immune response. In this context, iron is naturally associated with cancer occurrence. Cellular iron deficiency can induce apoptosis, however, iron can also engage in potentially harmful reactions that produce free radicals because of its capacity to gain and lose electrons. Studies suggest that dietary iron, particularly heme iron, may be one of the leading causes of colorectal cancer (CRC). Moreover, patients with CRC have abnormal iron absorption, storage, utilization, and exportation. Therefore, iron is crucial for the development and progression of CRC. Elaborating on the alterations in iron metabolism during the onset and advancement of CRC would help to further explain the role and mechanism of iron inside the body. Thus, we reviewed the alterations in numerous iron metabolism-related molecules and their roles in CRC, which may provide new clues between iron metabolism and CRC.

p120 RasGAP and ZO-2 are essential for Hippo signaling and tumor-suppressor function mediated by p190A RhoGAP.

ARHGAP35, which encodes p190A RhoGAP (p190A), is a major cancer gene. p190A is a tumor suppressor that activates the Hippo pathway. p190A was originally cloned via direct binding to p120 RasGAP (RasGAP). Here, we determine that interaction of p190A with the tight-junction-associated protein ZO-2 is dependent on RasGAP. We establish that both RasGAP and ZO-2 are necessary for p190A to activate large tumor-suppressor (LATS) kinases, elicit mesenchymal-to-epithelial transition, promote contact inhibition of cell proliferation, and suppress tumorigenesis. Moreover, RasGAP and ZO-2 are required for transcriptional modulation by p190A. Finally, we demonstrate that low ARHGAP35 expression is associated with shorter survival in patients with high, but not low, transcript levels of TJP2 encoding ZO-2. Hence, we define a tumor-suppressor interactome of p190A that includes ZO-2, an established constituent of the Hippo pathway, and RasGAP, which, despite strong association with Ras signaling, is essential for p190A to activate LATS kinases.

Construction and validation of a glycolysis-related lncRNA signature for prognosis prediction in Stomach Adenocarcinoma.

Background: Glycolysis is closely related to the occurrence and progression of gastric cancer (GC). Currently, there is no systematic study on using the glycolysis-related long non-coding RNA (lncRNA) as a model for predicting the survival time in patients with GC. Therefore, it was essential to develop a signature for predicting the survival based on glycolysis-related lncRNA in patients with GC. Materials and methods: LncRNA expression profiles, containing 375 stomach adenocarcinoma (STAD) samples, were obtained from The Cancer Genome Atlas (TCGA) database. The co-expression network of lncRNA and glycolysis-related genes was used to identify the glycolysis-related lncRNAs. The Kaplan-Meier survival analysis and univariate Cox regression analysis were used to detect the glycolysis-related lncRNA with prognostic significance. Then, Bayesian Lasso-logistic and multivariate Cox regression analyses were performed to screen the glycolysis-related lncRNA with independent prognostic significance and to develop the risk model. Patients were assigned into the low- and high-risk cohorts according to their risk scores. A nomogram model was constructed based on clinical information and risk scores. Gene Set Enrichment Analysis (GSEA) was performed to visualize the functional and pathway enrichment analyses of the glycolysis-related lncRNA. Finally, the robustness of the results obtained was verified in an internal validation data set. Results: Seven glycolysis-related lncRNAs (AL353804.1, AC010719.1, TNFRSF10A-AS1, AC005586.1, AL355574.1, AC009948.1, and AL161785.1) were obtained to construct a risk model for prognosis prediction in the STAD patients using Lasso regression and multivariate Cox regression analyses. The risk score was identified as an independent prognostic factor for the patients with STAD [HR = 1.315, 95% CI (1.056-1.130), p < 0.001] via multivariate Cox regression analysis. Receiver operating characteristic (ROC) curves were drawn and the area under curve (AUC) values of 1-, 3-, and 5-year overall survival (OS) were calculated to be 0.691, 0.717, and 0.723 respectively. Similar results were obtained in the validation data set. In addition, seven glycolysis-related lncRNAs were significantly enriched in the classical tumor processes and pathways including cell adhesion, positive regulation of vascular endothelial growth factor, leukocyte transendothelial migration, and JAK_STAT signaling pathway. Conclusion: The prognostic prediction model constructed using seven glycolysis-related lncRNA could be used to predict the prognosis in patients with STAD, which might help clinicians in the clinical treatment for STAD.

The Regulatory Network of MicroRNA in the Metabolism of Colorectal Cancer.

Colorectal cancer (CRC) is the third most common malignant tumor in the world. During the progression of CRC, the entire metabolic network undergoes reprogramming, including marked changes in the regulation of glucose, lipid and amino acid metabolism. Although microRNAs (miRNAs) account for only 1% of the entire human genome, they play an important role in almost all physiological and pathological processes in the body. MiRNAs can react directly with key enzymes in the metabolic processes. MiRNAs also interact with other ncRNAs, as a member of non-coding RNA (ncRNA), to form their own regulatory network in various oncogenic pathways of CRC metabolism. The progression of colorectal cancer is closely related to the intestinal flora, where miRNAs act as important mediators. Understanding how miRNAs act in the regulatory network of CRC metabolism is helpful to elucidate the characteristics of tumor occurrence, proliferation, metastasis and drug resistance. This review summarizes the role of miRNAs in the metabolism of CRC and how miRNAs interact with key enzymes, ncRNA and intestinal flora to further discuss how miRNAs affect CRC and realize some new strategies for the early diagnosis and treatment of CRC.

[Lumbar facet joint degeneration contributes to degenerative lumbar scoliosis induced by asymmetric stress in rabbits].

OBJECTIVE: To investigate the role of lumbar facet joint degeneration in the development of degenerative lumbar scoliosis caused by asymmetric stress. METHODS: Thirty-six New Zealand white rabbits were randomly divided into 3 groups (n=12): Group A with aspiration of the nucleus pulposus to induce disc degeneration; Group B with removal of the left capsule from the facet joints at L3/4 to L5/6 to induce degeneration; and Group C with both treatments. Springs were deployed on the left adjacent facets at L3/4, L5/6 and L5/6 to stress the facet joints. Serial radiographs were taken at 3 and 6 months, and the facet joint tissues were sampled at 6 months for Safranin O-fast green staining to assess the severity of cartilage degeneration based on the Mankin score. RESULTS: The Cobb angle differed significantly among the 3 groups (F=24.865, P=0.000). In all the groups, the Cobb angles at 6 months increased significantly as compared with that at 3 months (P <0.05). The Cobb angles were significantly greater in group C than in the other 2 groups at both 3 and 6 months (P <0.05) but showed no significant difference between Groups A and B (P>0.05). The severity of facet joint degeneration also differed significantly among the 3 groups (F= 22.009, P=0.000), and was the most severe in group C (P <0.05); facet joint degeneration was more severe in group B than in group A (P <0.05). CONCLUSIONS: Facet joint degeneration is an important factor that contributes to the development of degenerative lumbar scoliosis. Disc degeneration and facet joints degeneration can lead to lumbar scoliosis, which in turn aggravates disc degeneration, facet joints degeneration and asymmetric stress, thus forming a vicious circle to further exacerbate lumbar scoliosis.