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Colorectal cancer (CRC) is still one of the leading causes of cancer-associated death in the modern society. The biological function of miR-202-5p for CRC development remains controversial, largely due to the fact that miR-202-5p can be tumor-suppressive or oncogenic in different contexts. Obtained results indicated that aberrant expression of miR-202-5p was observed in majority of human CRC samples and miR-202-5p was transcriptionally up-regulated by c-Myc. In addition, miR-202-5p functions to promote the activation of PI3K/Akt signaling pathway by directly suppressing PTEN. Silencing or enforced expression of miR-202-5p resulted in CRC cell proliferation inhibition and enhancement, respectively. Importantly, decreased PTEN level and increased phosphorylation of Akt were frequently associated with elevated miR-202-5p expression in colorectal cancer tissues. Increased miR-202-5p expression may serve as a tumor promoter by directly targeting PTEN in colorectal cancer.

Fascin actin-bundling protein 1 (FSCN1) is an actin-bundling protein that is capable of inducing membrane protrusions and plays critical roles in cell migration, motility, adhesion, and other cellular interactions. FSCN1 also plays a role in forming and stabilizing filopodia or microspikes, which assist during cell migration. Furthermore, FSCN1 is a downstream target of several microRNAs and participates in various biological processes, such as epithelial-to-mesenchymal transition and autophagy, which regulate the invasion and migration ability of cells in various cancers. Increased FSCN1 levels have been associated with enhanced migration and invasion of multiple cancers as well as poor patient prognosis. Promising results from

Radioresistance is a major cause of treatment failure in tumor radiation therapy, and the underlying mechanisms of radioresistance are still elusive. Golgi phosphoprotein 3 (GOLPH3) has been reported to associate tightly with cancer progression and chemoresistance. Herein, we explored whether GOLPH3 mediated radioresistance of lung adenocarcinoma (LUAD) and whether targeted suppression of GOLPH3 sensitized LUAD to radiation therapy.The aberrant expression of GOLPH3 was evaluated by immunohistochemistry in LUAD clinical samples. To evaluate the association between GOLPH3 and radioresistance, colony formation and apoptosis were assessed in control and GOLPH3 knockdown cells. γ-H2AX foci and level determination and micronucleus test were used to analyze DNA damage production and repair. The rescue of GOLPH3 knockdown was then performed by exogenous expression of small interfering RNA-resistant mutant GOLPH3 to confirm the role of GOLPH3 in DNA damage repair. Mechanistically, the effect of GOLPH3 on regulating stability and nuclear accumulation of epidermal growth factor receptor (EGFR) and the activation of DNA-dependent protein kinase (DNA-PK) were investigated by quantitative real-time polymerase chain reaction, western blot, immunofluorescence, and coimmunoprecipitation. The role of GOLPH3 in vivo in radioresistance was determined in a xenograft model.In tumor tissues of 33 patients with LUAD, the expression of GOLPH3 showed significant increases compared with those in matched normal tissues. Knocking down GOLPH3 reduced the clonogenic capacity, impaired double-strand break (DSB) repair, and enhanced apoptosis after irradiation. In contrast, reversal of GOLPH3 depletion rescued the impaired repair of radiation-induced DSBs. Mechanistically, loss of GOLPH3 accelerated the degradation of EGFR in lysosome, causing the reduction in EGFR levels, thereby weakening nuclear accumulation of EGFR and attenuating the activation of DNA-PK. Furthermore, adenovirus-mediated GOLPH3 knockdown could enhance the ionizing radiation response in the LUAD xenograft model.GOLPH3 conferred resistance of LUAD to ionizing radiation via stabilizing EGFR, and targeted suppression of GOLPH3 might be considered as a potential therapeutic strategy for sensitizing LUAD to radiation therapy.

// Haili Wu 1 , Peng Yang 1 , Wanglai Hu 3 , Yingying Wang 1 , Yangxu Lu 4 , Lichao Zhang 1 , Yongsheng Fan 2 , Hong Xiao 5 , Zhuoyu Li 1, 2 1 Institute of Biotechnology, Key Laboratory of Chemical Biology and Molecular Engineering of National Ministry of Education, Shanxi University, Taiyuan 030006, China 2 College of Life Science, Zhejiang Chinese Medical University, Hangzhou 310053, China 3 Department of Immunology, School of Basic Medicine, Anhui Medical University, Hefei 230032, China 4 College of Life Science, Shanxi University, Taiyuan 030006, China 5 The first hospital of Shanxi Medical University, Taiyuan 030006, China Correspondence to: Haili Wu, email: wuhaili0819@163.com Zhuoyu Li, email: lzy@sxu.edu.cn Keywords: PKM2, Drp1, mitochondrial fusion, p53 stability Received: January 28, 2016 Accepted: October 16, 2016 Published: October 27, 2016 ABSTRACT M2-type pyruvate kinase (PKM2) contributes to the Warburg effect. However, it remains unknown as to whether PKM2 has an inhibitory effect on mitochondrial function. We report in this work that PKM2 overexpression inhibits the expression of Drp1 and results in the mitochondrial fusion. The ATP production was found to be decreased, the mtDNA copy number elevated and the expression level of electron transport chain (ETC) complex I, III, V depressed in PKM2 overexpressed cells. PKM2 overexpression showed a decreased p53 protein level and a shorter p53 half-life. In contrast, PKM2 knockdown resulted in increased p53 expression and prolonged half-life of p53. PKM2 could directly bind with both p53 and MDM2 and promote MDM2-mediated p53 ubiquitination. The dimeric PKM2 significantly suppressed p53 expression compared with the other PKM2 mutants. The reverse relationship between PKM2 and Drp1 was further confirmed in a large number of clinical samples. Taken together, the present results highlight a new mechanism that link PKM2 to mitochondrial function, based on p53-Drp1 axis down regulation, revealing a novel therapeutic target in patients with abnormal mitochondria.

// Qun Li 1, * , Yan Zhu 2, * , Lili Hou 3, * , Juan Wang 4 , Guilin Hu 5 , Xing Fang 6 , Yamin Hu 6 , Tingting Tao 6 , Xin Wei 6 , Haitao Tang 6 , Baojun Huang 1 , Wanglai Hu 1 1 Department of Immunology, Anhui Medical University, Hefei, China 2 Department of Anesthesiology, The First Affiliated Hospital of Anhui Medical University, Hefei, China 3 Department of Clinical Nutriology, The First Affiliated Hospital of Anhui Medical University, Hefei, China 4 Department of Molecular Biology, Shanxi Cancer Hospital and Institute, Affiliated Hospital of Shanxi Medical University, Taiyuan, China 5 School of Life Sciences, Anhui Medical University, Hefei, China 6 School of Pharmacy, Anhui Medical University, Hefei, China * These authors have contributed equally to this work Correspondence to: Wanglai Hu, email: wanglaihu@ahmu.edu.cn Keywords: C23, p53, tumorigenesis Received: February 03, 2016 Accepted: July 18, 2016 Published: August 05, 2016 ABSTRACT C23 is an abundant and multi-functional protein, which plays an important role in various biological processes, including ribosome biogenesis and maturation, cell cycle checkpoints and transcriptional regulation [ 1 , 2 ]. However, the role of C23 in controlling tumorigenesis has not been well defined. Here we report that C23 is highly expressed in cancer cells and the elevated expression of C23 facilitates cancer cell proliferation in vitro and tumor xenograft growth in vivo . Notably, C23 binds to p53 through its GAR domain and suppresses the transcriptional activity of p53 under DNA damage and hypoxia. Moreover, the GAR domain is critical for C23-mediated tumor cell proliferation both in vitro and in vivo . Our findings reveal a novel role of C23 in tumorigenesis and suggest that C23 may represent a potential therapeutic target for treating malignancy.

Isocitrate dehydrogenase1 (IDH1) is of great importance in cell metabolism and energy conversion. However, alterations in IDH1 in response to stress and excise-regulated mechanisms are not well described. Here we investigated gene expression profiles under ER stress in melanoma cells and found that IDH1 was dramatically increased with ER stress induced by tunicamycin. Elevated IDH1 subsequently sensitized human melanoma cells to hypoxia-induced apoptosis and promoted HIF-1α degradation. In addition, we revealed that CHOP and C/EBPβ were involved in hypoxia-induced apoptosis via transcriptional regulation of IDH1 expression. Our data indicate that IDH1, regulated by CHOP and C/EBPβ in response to ER stress treatment, inhibits survival of melanoma cells under hypoxia and promotes HIF-1α degradation. Therefore, we propose that IDH1 may serve as a valuable target for melanoma therapy.

// Wu Shuang 1, * , Lili Hou 2, * , Yan Zhu 3, * , Qun Li 1 and Wanglai Hu 1 1 Department of Immunology, Anhui Medical University, Hefei, China 2 Department of Clinical Nutriology, The First Affiliated Hospital of Anhui Medical University, Hefei, China 3 Department of Anesthesiology, The First Affiliated Hospital of Anhui Medical University, Hefei, China * These authors have contributed equally to this work Correspondence to: Wanglai Hu, email: wanglaihu@ahmu.edu.cn Keywords: Mcl-1, PI3K/Akt, Taxol-resistance Received: March 08, 2017 Accepted: July 26, 2017 Published: August 12, 2017 ABSTRACT Taxol has been extensively used as an antineoplastic drug to treat human gastric cancer. However, the acquired drug resistance invariably develops and greatly limits the therapeutic efficacy of Taxol. Identification of the underlying resistance mechanisms may inform the development of new therapies of gastric cancers to Taxol treatment. Here we report that upregulation of Mcl-1 (Myeloid cell leukemia-1) confers acquired resistance to Taxol in human gastric cancer. Mcl-1 is shown to be stabilized in Taxol -resistant gastric cancer cells because of the hyper-activation of the PI3K/Akt signaling pathway. The increased Mcl-1 prevents of the permeabilization of the outer mitochondrial membrane, thereby blocking the Taxol-induced apoptosis. Furthermore, inhibition of Mcl-1 or PI3K/Akt pathway significantly reversed the resistant phenotype of Taxol-resistant human gastric cancer cells. Taken together, our findings broaden the view of PI3K/Akt pathway as an important regulator in Taxol acquired resistance, and implicate Mcl-1 as a specific therapeutic target for the treatment of Taxol-resistant human gastric cancer.