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Metabolism reprogramming is a hallmark of many cancer types. We focused on clear cell renal carcinoma (ccRCC) which is characterized by its clear and glycogen-enriched cytoplasm with unknown reasons. The aim of this study was to identify the clinical significance, biological function, and molecular regulation of glycogen synthase 1 (GYS1) in ccRCC glycogen accumulation and tumor progression. Methods: We determined the clinical relevance of GYS1 and glycogen in ccRCC by immunohistochemistry and periodic acid-schiff staining in fresh tissue and by tissue micro-array. Metabolic profiling with GYS1 depletion was performed by metabolomics analysis. In vitro and xenograft mouse models were used to evaluate the impact of GYS1 on cell proliferation. High-throughput RNA-Seq analyses and co-immunoprecipitation-linked mass spectrometry were used to investigate the downstream targets of GYS1. Flow cytometry and CCK8 assays were performed to determine the effect of GYS1 and sunitinib on cell viability. Results: We observed that GYS1 was significantly overexpressed and glycogen was accumulated in ccRCC tissues. These effects were correlated with unfavorable patient survival. Silencing of GYS1 induced metabolomic perturbation manifested by a carbohydrate metabolism shift. Overexpression of GYS1 promoted tumor growth whereas its silencing suppressed it by activating the canonical NF-κB pathway. The indirect interaction between GYS1 and NF-κB was intermediated by RPS27A, which facilitated the phosphorylation and nuclear import of p65. Moreover, silencing of GYS1 increased the synthetic lethality of ccRCC cells to sunitinib treatment by concomitantly suppressing p65. Conclusions: Our study findings reveal an oncogenic role for GYS1 in cell proliferation and glycogen metabolism in ccRCC. Re-sensitization of ccRCC cells to sunitinib suggests that GYS1 is a useful indicator of unfavorable prognosis as well as a therapeutic target for patients with ccRCC.

BackgroundMicroRNAs are non-coding RNAs which regulate a variety of cellular functions in the development of tumors. Among the numerous microRNAs, microRNA-30a (miR-30a) is thought to play an important role in the processes of various human tumors. In this study, we aimed to explore the role of miR-30a in the process of colorectal cancer (CRC).MethodsThe quantitative real-time PCR and western blot analysis were used to detect the expressions of miR-30a and CD73 in CRC cell lines and clinical tissues. The luciferase reporter assay was conducted to validate the association between miR-30a and CD73. The CCK-8, terminal deoxynucleotidyl transferase dUTP -biotin nick end labeling (TUNEL) assays and cell cycle flow cytometry were carried out to verify the biological functions of miR-30a in vitro. The nude mouse tumorigenicity experiment was used to clarify the biological role of miR-30a in vivo.ResultsThe expression of miR-30a was significantly reduced in tumor cells and tissues of CRC. The proliferation ability of CRC cells was suppressed and the apoptosis of cells was promoted when miR-30a is over-regulated, however, the biological effects would be inverse since the miR-30a is down-regulated. CD73 is thought to be a target binding gene of miR-30a because miR-30a can bind directly to the 3′-UTR of CD73 mRNA, subsequently reducing its expression. The proliferation suppression of the CRC cells mediated by miR-30a could be rescued after up-regulating the expression of CD73.ConclusionsMiR-30a plays an important role on regulating the cell proliferation and apoptosis, thus affecting the growth of the tumor in CRC. And it may participate in the disease process of CRC by regulating the expression of CD73.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-017-3291-8) contains supplementary material, which is available to authorized users.

Background and objective Neoadjuvant chemoradiation therapy (NCRT) followed by radical resection has been a common practice for patients with locally advanced rectal cancer. This study aimed to analyse the association of tumor differentiation and prognosis in rectal-cancer patients undergoing NCRT. Methods Patients with locally advanced, non-mucinous rectal cancer who underwent NCRT followed by radical resection between 2007 and 2017 were identified from an electronic health record system at the Sixth Affiliated Hospital of Sun Yat-sen University (Guangzhou, China). Multivariable logistic regression and multivariate Cox regression were performed to analyse the association of response to NCRT and survival with clinicopathological characteristics of all these patients. Results We identified 325 patients (241 males and 84 females; mean age, 54.4 ± 11.2 years) who underwent NCRT followed by radical resection, including 26 (8.0%) with poorly-differentiated rectal cancer, 182 (56.0%) with moderately-differentiated cancer and 117 (36.0%) with well differentiated cancer. Propensity score matching analysis and multivariable logistic regression analysis results showed that tumor differentiation was significantly associated with response to NCRT. In the poor differentiation and non-poor differentiation groups, the 3-year overall survival (OS) rates were 74.6 and 93.5%, respectively, whereas the 3-year local recurrence rates were 18.6 and 3.7%, respectively. Multivariable Cox regression analyses revealed that poor differentiation was an independent risk factor for local recurrence and OS. Conclusions Among the patients with locally advanced, non-mucinous rectal cancer, the patients with poorly-differentiated cancer who underwent NCRT had a worse response to NCRT and poorer prognosis than those with moderately- and well-differentiated diseases.

MSCs exert anti-fibrogenic activity against CD-associated fibrosis by regulating the inflammatory environment, inhibiting the TGF-beta/Smad signaling pathway and ameliorating EMT.