These findings suggested that SNRPA may contribute to GC progression via NGF and could be a prognostic biomarker for GC.

ADAR1, one of adenosine deaminases acting on RNA, modulates RNA transcripts through converting adenosine (A) to inosine (I) by deamination. Emerging evidence has implicated that ADAR1 plays an important role in a few of human cancers, however, its expression and physiological significance in gastric cancer remain undefined. In the present study, we demonstrated that ADAR1 was frequently overexpressed in gastric cancer samples by quantitative real-time PCR analysis. In a gastric cancer tissue microarray, ADAR1 staining was closely correlated with tumor stage (P < 0.001) and N classification (P < 0.001). Functional analysis indicated that ADAR1 overexpression promoted cell proliferation and migration in vitro, whereas ADAR1 knockdown resulted in an opposite phenotypes. Furthermore, ADAR1 knockdown also inhibited tumorigenicity and lung metastasis potential of gastric cancer cells in nude mice models. Mechanistically, ADAR1 expression had a significant effect on phosphorylation level of mTOR, p70S kinase, and S6 ribosomal protein, implying its involvement in the regulation of mTOR signaling pathway. We conclude that ADAR1 contributes to gastric cancer development and progression via activating mTOR/p70S6K/S6 ribosomal protein signaling axis. Our findings suggest that ADAR1 may be a valuable biomarker for GC diagnosis and prognosis and may represent a new novel therapeutic opportunities.

Objective: To assess the clinical and radiological outcomes following unilateral or bilateral approach in percutaneous kyphoplasty (PKP) for treatment of osteoporotic vertebral compression fractures (OVCF). Design: Prospective comparative study. Setting: University affiliated hospital. Paricipants: From 2012 through 2016, those MRI-diagnosed single-level lumbar OVCF patients. Interventions: They were randomly assigned for treatment with unilateral or bilateral PKP. Outcome measures: We assessed the patient' health status with the Oswestry Disability Index (ODI) questionnaire. Anteroposterior and lateral standing radiographs were obtained to measure the vertebral height and kyphotic angle of the vertebral body in all patients. Results: Eighty-five patients were finally enrolled in this investigation, including 42 in the unilateral and 43 in the bilateral group. The operation time,

USP32, a member of the ubiquitin-specific proteases family, has been implicated in the development of breast cancer and small lung cancer. However, its biological functions and clinical significance in gastric cancer (GC) remain unclear. In the present study, we reported that knockdown or depletion of USP32 significantly inhibited GC cell proliferation and migration in vitro and in vivo, indicating that USP32 functions as an oncogene in GC. Importantly, results from immunohistochemical staining in a tissue microarray revealed that USP32 was upregulated in GC tissues compared with paracancerous tissues. Further analyses showed that high expression of USP32 was closely related with high T-staging and poor outcomes of GC patients. Mechanistically, USP32 silencing caused a decrease in the expression of SMAD2, which resulted in the inhibitory effects of GC cells on growth, motility, and chemoresistance to cisplatin. Therefore, our findings strongly suggest the involvement of USP32 in GC progression and provide a potential target for future therapy of GC.

Aim B‐cell lymphoma‐2‐associated transcription factor 1 (BCLAF1) is involved in various biological processes including tumorigenesis, but its function and expression in hepatocellular carcinoma (HCC) is little known, and its clinical value in HCC has not yet been defined. Methods The protein level of BCLAF1 in HCC specimens and paired adjacent normal tissues was examined by immunohistochemical staining. The effects of BCLAF1 on autophagy in HCC cells were detected by confocal microscopy, transmission electron microscopy, and western blot analysis. Cell proliferation and tumorigenicity assays were carried out in vitro and in vivo. Flow cytometry assay was used to determine the apoptosis level of HCC cells. The correlation of BCLAF1 and sorafenib resistance in HCC was analyzed by the Kaplan–Meier survival method. Results High expression of BCLAF1 was found in HCC tissues compared with adjacent normal tissues, and higher BCLAF1 expression was correlated with higher tumor–node–metastasis stage, worse differentiation, and worse prognosis of HCC patients. BCLAF1 could induce autophagy in HCC cells in response to starvation and BCLAF1‐mediated autophagy could enhance cell proliferation and impede cell apoptosis under stress conditions. Animal experiments indicated that BCLAF1 promoted tumorigenicity of HCC cells in vivo. More importantly, high expression of BCLAF1 might contribute to sorafenib resistance in HCC patients. Conclusions BCLAF1 is a potential oncogene in HCC by inducing autophagy to maintain tumor cell growth in response to stress conditions, and it could serve as a potential biomarker for predicting the prognosis of HCC patients and screening patients who are suitable for sorafenib therapy.

Protein phosphatase 2A (PP2A) is an essential serine/threonine protein phosphatase that regulates the basic activities of eukaryotes by dephosphorylating its substrates. The function and substrate specificity of PP2A are generally determined by its regulatory subunits. In the present study, the clinical significance and roles of PPP2R2D, one of the regulatory subunits of PP2A, were demonstrated in gastric cancer (GC) carcinogenesis. Through a tissue microarray and quantitative polymerase chain reaction analysis, it was demonstrated that PPP2R2D was commonly upregulated in GC samples. This upregulation was positively correlated with the patients' tumor stage (P<0.01), T classification (P<0.01) and N classification (P=0.01). Furthermore, a high expression of PPP2R2D was closely associated with poor prognosis of patients. Knockdown of PPP2R2D significantly inhibited the proliferation and migration of GC cells in vitro, as well as the tumorigenicity and metastasis in vivo in an animal GC model. By contrast, overexpression of PPP2R2D promoted GC cell proliferation and migration in vitro. The analysis of underlying mechanisms indicated that PPP2R2D silencing decreased the phosphorylation level of mechanistic target of rapamycin (mTOR), thereby implicating that PPP2R2D is involved in the regulation of mTOR activity during tumorigenesis. Thus, the findings of the present study suggested that PPP2R2D may serve as a potential oncogene in GC and as a novel target for therapeutic strategies against this disease.

P-cadherin (CDH3), a classical cell adhesion molecule involved in tissue integrity and cell localization, has been implicated in many types of cancer. However, little is known about its function and regulatory mechanism in hepatocellular carcinoma (HCC). Here we report that CDH3 was positively regulated by kr¨uppel-like transcription factor 4 (KLF4), which is a crucial tumor suppressor gene in HCC, at mRNA level in HCC cell lines. Luciferase reporter assay and chromatin immunoprecipitation assay indicated that KLF4 directly bound to CDH3 promoter and transcriptionally activated CDH3 expression. Consistently, CDH3 expression was closely related with KLF4 expression in patients' samples and both proteins exhibited a downregulated expression pattern in cancer samples. Functionally, enforced CDH3 expression suppressed and silenced CDH3 expression promoted HCC cell growth and migration in vitro . Mechanistically, we observed that GSK-3β was regulated by CDH3 and may function as a possible downstream effector of CDH3. Knockdown of GSK-3β showed a similar phenotype with CDH3 silencing. Taken together, these findings establish the KLF4/CDH3/GSK-3β axis as an important regulatory mechanism in HCC development.

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