ADAM metallopeptidase with thrombospondin type 1 motif 16 is a potential marker for prognosis in clear cell renal cell carcinoma.

The mortality rate of clear cell renal cell carcinoma (ccRCC) remains high. Immunohistochemical staining, Western blotting and real-time quantitative polymerase chain reaction were employed to evaluate ADAM (a disintegrin and metalloproteinase) metallopeptidase with thrombospondin type 1 motif 16 (ADAMTS16) levels in ccRCC tissues and paired normal tissues, and all tissues were obtained from clinical samples of 46 cases of ccRCC patients. Moreover, we analyzed the role ADAMTS16 in the progression of ccRCC using Cell Counting Kit-8 assay and flow cytometry. ADAMTS16 levels in ccRCC tissues were markedly low, relative to normal tissues, and ADAMTS16 level closely correlated with tumor stage, lymph node metastasis as well as pathological grade. Patients with elevated ADAMTS16 expressions have a more favorable survival outcome, relative to patients with low expression of ADAMTS16. In vitro study showed ADAMTS16 expression markedly decreased in ccRCC cells and acted as a tumor suppressor compared with the normal cells. The expression of ADAMTS16 is down-regulated in ccRCC tissues, relative to normal tissues, and it may inhibit the malignancies of ccRCC. Such inhibitory effect may be ascribed to the involvement of AKT/mammalian target of rapamycin signaling. Hence, the present study of ADAMTS16 will provide new insight into the underlying biological mechanisms of ccRCC.

Prognosis and Novel Drug Targets for Key lncRNAs of Epigenetic Modification in Colorectal Cancer.

Background: Colorectal cancer (CRC) has been the 3rd most commonly malignant tumor of the gastrointestinal tract in the world. 5-Methylcytosine (m5C) and long noncoding RNAs (lncRNAs) have an essential role in predicting the prognosis and immune response for CRC patients. Therefore, we built a m5C-related lncRNA (m5CRlncRNA) model to investigate the prognosis and treatment methods for CRC patients. Methods: Firstly, we secured the transcriptome and clinical data for CRC from The Cancer Genome Atlas (TCGA). Then, m5CRlncRNAs were recognized by coexpression analysis. Then, univariate Cox, least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analyses were utilized to build m5C-related prognostic characteristics. Besides, Kaplan-Meier analysis, ROC, PCA, C-index, enrichment analysis, and nomogram were performed to investigate the model. Additionally, immunotherapy responses and antitumor medicines were explored for CRC patients. Results: A total of 8 m5C-related lncRNAs (AC093157.1, LINC00513, AC025171.4, AC090948.2, ZEB1-AS1, AC109449.1, AC009041.3, and LINC02516) were adopted to construct a risk model to investigate survival and prognosis for CRC patients. CRC samples were separated into low- and high-risk groups, with the latter having a worse prognosis. The m5C-related lncRNA model helps us to better distinguish immunotherapy responses and IC50 of antitumor medicines in different groups of CRC patients. Conclusion: The research may give new perspectives on tailored therapy approaches as well as novel theories for forecasting the prognosis of CRC patients.

AKT1 phosphorylates RBM17 to promote Sox2 transcription by modulating alternative splicing of FOXM1 to enhance cancer stem cell properties in colorectal cancer cells.

Colorectal cancer (CRC) is one of the leading causes of cancer-related death worldwide. The existence of cancer stem cells (CSC) causes tumor relapses, metastasis, and resistance to conventional therapy. Alternative splicing has been shown to affect physiological and pathological processes. Accumulating evidence has confirmed that targeting alternative splicing could be an effective strategy to treat CRC. Currently, the role of alternative splicing in the regulation of CSC properties in CRC has not been elucidated. Here, we show that RBM17 displays oncogenic roles in CRC cells. RBM17 enhances cell proliferation and reduces chemotherapeutic-induced apoptosis in CRC cells. Besides, RBM17 increases CD133 positive and ALDEFLUOR positive populations and promotes sphere formation in CRC cells. In mechanism studies, we found that FOXM1 is critical for RBM17 enhanced CSC properties. Moreover, FOXM1 alternative splicing is essential for RBM17 enhanced CSC properties in CRC cells. Additionally, RBM17 enhances CSC characteristics by controlling FOXM1 expression to promote Sox2 expression. Furthermore, AKT1 works as an upstream kinase to control RBM17-mediated FOXM1 alternative splicing and enhancement of CSC properties in CRC cells. Our study reveals that AKT1-RBM17-FOXM1-Sox2 axis could be a potential target for modulating alternative splicing to reduce CSC properties in CRC cells.

NRCAM acts as a prognostic biomarker and promotes the tumor progression in gastric cancer via EMT pathway.

OBJECTIVE: Herein, we purposed to explore the NRCAM expression in gastric cancer (GC) along with its clinical implication. METHODS: The TCGA dataset was utilized to analyze the expression coupled with the clinical worthiness of NRCAM in GC. The expressions of NRCAM were examined in clinical GC specimens via qRT-PCR along with western blotting. Moreover, we analyzed the role NRCAM in the progression of GC using flow cytometry, Wound-healing, CCK-8, as well as Transwell assays. EMT markers (E-cadherin, vimentin along with N-cadherin) protein expression were examined via western blotting. RESULTS: TCGA data resource revealed that NRCAM expression in GC tissues is much lower in contrast with normal tissues and patients with higher NRCAM expression showed poorer prognosis. In vitro study revealed that the over-expression NRCAM accelerated cell growth, migration, as well as infiltration while decreasing cell apoptosis but silencing of NRCAM had the opposite effect. Upregulation of NRCAM reduced E-cadherin contents, however elevated vimentin coupled with N-cadherin protein levels in GC cells. Nonetheless, NRCAM downregulation led to the opposite results. CONCLUSION: According to our findings, NRCAM is an oncogene with the potential to works as a prognostic biomarker and treatment target for GC.

Clinicopathological Implication of Long Non-Coding RNAs SOX2 Overlapping Transcript and Its Potential Target Gene Network in Various Cancers.

BACKGROUND: SOX2 overlapping transcript (SOX2-OT) produces alternatively spliced long non-coding RNAs (lncRNA). Previous studies of the prognostic role of SOX2-OT expression met with conflicting results. The aim of this study was to properly consider the prognostic role of SOX2-OT expression in several cancers. In addition, the regulative mechanism of SOX2-OT is explored. METHODS: PubMed, EMBASE, and Cochrane Library and The Cancer Genome Atlas (TCGA) database were comprehensively explored to recover pertinent studies. We conducted an extensive inquiry to verify the implication of SOX2-OT expression in cancer patients by conducting a meta-analysis of 13 selected studies. Thirty-two TCGA databases were used to analyze the connection between SOX2-OT expression and both the overall survival (OS) and clinicopathological characteristics of cancer patients using R and STATA 13.0. Trial sequential analysis (TSA) was adopted in order to compute the studies' power. RESULTS: Thirteen studies involving 1172 cancer patients and 32 TCGA cancer types involving 9676 cancer patients were eventually selected. Elevated SOX2-OT expression was significantly related to shorter OS (HR = 2.026, 95% CI: 1.691-2.428, P < 0.0001) and disease-free survival (DFS) (HR = 2.554, 95% CI: 1.261-5.174, P = 0.0092) in cancer patients. Meanwhile, TSA substantiated adequate power to demonstrate the relationship between SOX2-OT expression and OS. The cancer patients with elevated SOX2-OT expression were more likely to have advanced clinical stage (RR = 1.468, 95% CI: 1.106-1.949, P = 0.0079), earlier lymphatic metastasis (P = 0.0005), earlier distant metastasis (P < 0.0001), greater tumor size (P < 0.0001), and more extreme tumor invasion (P < 0.0001) compared to those with low SOX2-OT expression. Meta-regression and subgroup analysis revealed that follow-up time, sample type, and tumor type could significantly contribute to heterogeneity for survival outcomes. The follow-up time could significantly explain heterogeneity for tumor, node, metastasis (TNM) stage. Furthermore, up to 500 validated target genes were distinguished, and the gene oncology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses demonstrated that the validated targets of SOX2-OT were substantially enriched in cell adhesion, mRNA binding, and mRNA surveillance pathways. CONCLUSIONS: Elevated expression of SOX2-OT predicted a poor OS and DFS. Overexpression of SOX2-OT was correlated with more advanced tumor stage, earlier lymphatic metastasis, earlier distant metastasis, larger tumor size, and deeper tumor invasion. SOX2-OT-mediated cell adhesion, mRNA binding, or mRNA surveillance could be intrinsic mechanisms for invasion and metastasis.

[Effect of gastric bypass surgery on mRNA expression level of hepatic phosphoenolpyruvate carboxykinase in type 2 diabetic Goto-Kakizaki rats].

OBJECTIVE: To investigate the effects of gastric bypass surgery(GBP) on hepatic phosphoenolpyruvate carboxykinase(PEPCK) mRNA expression in type 2 diabetic Goto-Kakizaki rats. METHODS: Male GK rats were randomized into three groups: gastric bypass surgery(n=10), sham operation with diet restriction(n=10), and sham operation alone(n=10). Liver specimens of GK rats were collected during the intraoperative period for self-control study and 8 weeks after surgery. Fasting blood glucose, food intake, and body weight were recorded before surgery and 1, 2, 4, 8 weeks after surgery. The expression of PEPCK mRNA was measured by real-time PCR. RESULTS: The fasting plasma glucose level decreased from(17.6±2.1) mmol/L before surgery to(7.5±0.9) mmol/L 8 weeks after surgery in GBP group. The level of PEPCK mRNA decreased from 1.08±0.38 before surgery to 0.41±0.10 8 weeks after surgery, significantly lower than that in sham operation alone group(1.04±0.12)(P<0.01). The level of PEPCK mRNA in diet restriction group increased from 1.15±0.16 before surgery to 2.54±0.82 8 weeks after surgery(P<0.01). The expression of PEPCK mRNA in diet restriction was significantly higher than that in CBP group(P<0.01). CONCLUSIONS: GBP can significantly improve hyperglycemia in type 2 diabetic GK rat models, which may be associated with the decrease of hepatic PEPCK mRNA level.