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Yuan Yuan, Gao Haiying, Li Zhuo, Lu Ying, He Xin
Non-small cell lung cancer (NSCLC) is one of leading causes of cancer-related death worldwide. Long noncoding RNAs (lncRNAs) has been identified to modulate the tumorigenesis of NSCLC. However, the precise molecular mechanism of lncRNAs in the course is still unclear. Results showed that LINC00339 was significantly up-regulated in NSCLC tissue and cells, which indicated the poor prognosis of NSCLC patients. Loss-of-function experiments showed that LINC00339 silencing inhibited the proliferation and invasion, accelerated the apoptosis, and suppressed the tumor growth of NSCLC cells in vitro and in vivo...
June 12, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Xuena Cui, Jin'e Xu, Yuzhi Ji, Xiuhong Song, Junhuan Wang, Lijuan Zhang, Shengmei Yang, Yuanhua Ye
The present study aimed to investigate the expression of the forkhead box protein M1 (FOXM1) in the placenta of patients with preeclampsia, and its effect on trophoblasts. A total of 28 patients with preeclampsia and 30 patients without preeclampsia (controls) who underwent cesarean section and were admitted to the Affiliated Hospital of Qingdao University between June 2013 and September 2016 were enrolled in the present study. The expression of FOXM1 in placental tissues was examined by reverse transcription-quantitative polymerase chain reaction, western blotting and immunohistochemistry...
July 2018: Experimental and Therapeutic Medicine
Ya Zhang, Xiangxiang Zhou, Ying Li, Yangyang Xu, Kang Lu, Peipei Li, Xin Wang
TP53 pathway defects contributed to therapy resistance and adverse clinical outcome in chronic lymphocytic leukemia (CLL), which represents an unmet clinical need with few therapeutic options. Maternal embryonic leucine zipper kinase (MELK) is a novel oncogene, which plays crucial roles in mitotic progression and stem cell maintenance. OTSSP167, an orally administrated inhibitor targeting MELK, is currently in a phase I/II clinical trial in patients with advanced breast cancer and acute myeloid leukemia. Yet, no investigation has been elucidated to date regarding the oncogenic role of MELK and effects of OTSSP167 in chronic lymphocytic leukemia (CLL)...
June 12, 2018: Oncogene
Bharat Bhushan, John W Stoops, Wendy M Mars, Anne Orr, William C Bowen, Shirish Paranjpe, George K Michalopoulos
TCPOBOP (1,4-Bis [2-(3,5-Dichloropyridyloxy)] benzene) is a constitutive androstane receptor (CAR) agonist that induces robust hepatocyte proliferation and hepatomegaly without any liver injury or tissue loss. TCPOBOP-induced direct hyperplasia has been considered to be CAR-dependent with no evidence of involvement of cytokines or growth factor signaling. Receptor tyrosine kinases (RTKs), MET and EGFR, are known to play a critical role in liver regeneration after partial hepatectomy, but their role in TCPOBOP-induced direct hyperplasia, not yet explored, is investigated in the current study...
June 11, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Zhaohua Xiao, Yang Jia, Wenpeng Jiang, Zhou Wang, Zhiping Zhang, Yanyun Gao
BACKGROUND: Previous studies have elucidated that FOXM1 may predict poor prognosis in patients with multiple solid malignant tumors. In this study we explored the differential expression of FOXM1 in stage IIA esophageal squamous cell carcinoma (ESCC) and investigated its prognostic value. METHODS: Immunohistochemistry (IHC) and Western blot were used to detect FOXM1 expression in ESCC. Correlations between FOXM1 expression and clinicopathological variables, and five-year lymphatic metastatic recurrence (LMR) and overall survival (OS) of patients were analyzed...
June 6, 2018: Thoracic Cancer
Dong Zhu-Ge, Yu-Ping Yang, Zi-Jun Jiang
OBJECTIVE: Pneumonia is the leading global cause of mortality and morbidity in children and elderly people worldwide. The lncRNA colorectal neoplasia differentially expressed (CRNDE) plays an important role in the human development and disease progression. The present study was aimed to investigate the effect of CRNDE on LPS-induced injuries in WI-38 cells and explore the potential mechanism. METHODS: WI-38 cells were treated with LPS to induce injuries. The expression of CRNDE and FOXM1 in WI-38 cells were altered by transient transfection assay...
July 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Ruth M O'Regan, Rita Nahta
Breast cancer continues to be the most commonly diagnosed malignancy and second most common cause of cancer-related deaths among women in the United States. Improved understanding of the molecular heterogeneity of breast tumors and the approval of multiple targeted therapies have revolutionized the treatment landscape and long-term survival rates for patients with breast cancer. Despite the development of highly effective targeted agents, drug resistance and disease progression remain major clinical concerns...
May 31, 2018: Biochemical Pharmacology
Elisa Callegari, Lucilla D'Abundo, Paola Guerriero, Carolina Simioni, Bahaeldin K Elamin, Marta Russo, Alice Cani, Cristian Bassi, Barbara Zagatti, Luciano Giacomelli, Stella Blandamura, Farzaneh Moshiri, Simona Ultimo, Antonio Frassoldati, Giuseppe Altavilla, Laura Gramantieri, Luca Maria Neri, Silvia Sabbioni, Massimo Negrini
Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death worldwide. Prognosis is poor, and therapeutic options are limited. MicroRNAs (miRNAs) have emerged as potential therapeutic molecules against cancer. Here, we investigated the therapeutic efficacy of miR-199a-3p, an miRNA highly expressed in normal liver and downregulated in virtually all HCCs. The therapeutic value of miR-199a-3p mimic molecules was assayed in the TG221 mouse, a transgenic model highly predisposed to the development of liver cancer...
June 1, 2018: Molecular Therapy. Nucleic Acids
Lara J Monteiro, Sofia Cubillos, Marianela Sanchez, Stephanie Acuña-Gallardo, Pía Venegas, Valentina Herrera, Eric W-F Lam, Manuel Varas-Godoy, Sebastián E Illanes
Trophoblast cells are often compared to highly invasive carcinoma cells due to their capacity to proliferate in hypoxic conditions and to exhibit analogous vascular, proliferative, migratory, and invasive capacities. Thus, genes that are important for tumorigenesis, such as forkhead box M1 ( FOXM1) may also be involved in processes of trophoblast invasion. Indeed, we found Foxm1 protein and messenger RNA (mRNA) levels decreased as gestational age increased in rat's placentae. Accordingly, when mimicking early placental events in vitro, protein and mRNA expression of FOXM1 increased from 21% to 8% O2 , reaching its highest expression at 3% oxygen tension, which reflects early implantation environment, and dropping to very low levels at 1% O2 ...
January 1, 2018: Reproductive Sciences
Katherine Pfister, Justyna L Pipka, Colby Chiang, Yunxian Liu, Royden A Clark, Ray Keller, Paul Skoglund, Michael J Guertin, Ira M Hall, P Todd Stukenberg
Although aneuploidy is found in the majority of tumors, the degree of aneuploidy varies widely. It is unclear how cancer cells become aneuploid or how highly aneuploid tumors are different from those of more normal ploidy. We developed a simple computational method that measures the degree of aneuploidy or structural rearrangements of large chromosome regions of 522 human breast tumors from The Cancer Genome Atlas (TCGA). Highly aneuploid tumors overexpress activators of mitotic transcription and the genes encoding proteins that segregate chromosomes...
May 29, 2018: Cell Reports
Yi Zhang, Xiaojuan Ye, Lizhi Chen, Qiong Wu, Yong Gao, Yandong Li
PARI, an element of the homologous recombination pathway of DNA repair , is involved in the regulation of cell cycle and carcinogenesis in pancreatic cancer. However, little is known about the function and regulatory mechanism of PARI in other cancers. In the present study, we evaluated the expression of PARI in gastric cancer (GC) by immunohistochemical analysis in a tissue microarray and characterized its functions using in vitro assays and in vivo animal models. We found higher expression of PARI protein was shown in GC tissues compared with related adjacent normal gastric mucosa tissues...
2018: International Journal of Biological Sciences
Xiaoxiao Li, Kai Ma, Shanai Song, Fangzhen Shen, Tao Kuang, Yingqian Zhu, Zimin Liu
The aim of the present study was to investigate the expression of Forkhead box transcription M1 (FoxM1) and Forkhead box transcription P3 (FoxP3) in gastric cancer tissues in order to reveal any correlation between FoxM1, FoxP3 and clinicopathological parameters. Their clinical significance in gastric cancer was also investigated. Immunohistochemistry was used to detect the expression of FoxM1 and FoxP3 in gastric cancer and para-cancer tissues. The clinical significance of FoxM1 and FoxP3 in gastric cancer was explored, and the association between FoxM1 and FoxP3 was further analyzed...
May 26, 2018: Clinical and Experimental Medicine
Xiaorui Liu, Lei Zhang, Yuexia Liu, Jiuzeng Cui, Sicheng Che, Xiaopeng An, Yuxuan Song, Binyun Cao
Circular RNAs (circRNAs) are a large class of endogenous non-coding RNAs that function as regulators in various cells and tissues. Here, the function and mechanism of circRNA8073 (Circ-8073) on endometrial epithelial cells (EECs) and the development of endometrial receptivity were investigated in dairy goats. Circ-8073 could bind to and inhibit miR-449a activity. Circ-8073 binding to the target site of miR-449a had a negative feedback relationship. Centrosomal protein55 (CEP55) was a direct target gene of miR-449a, and Circ-8073 could increase the expression levels of CEP55 by sponging miR-449a in EECs in vitro...
May 22, 2018: Biochimica et Biophysica Acta
Jintaek Im, Jessica Lawrence, Davis Seelig, Richard S Nho
Radiation therapy is critical for the control of many tumors and lung is an important dose-limiting organ that impacts radiation dose prescribed to avoid irreversible pulmonary fibrosis in cancer survivors. Idiopathic pulmonary fibrosis (IPF) is a chronic, irreversible lung disease caused by aberrantly activated lung (myo)fibroblasts. The presence of pro-fibrotic, apoptosis-resistant fibroblasts in IPF promotes progressive fibrosis and may have a role in other diseases, if these resistant cells are selected for as a consequence of treatment...
May 22, 2018: Cell Death & Disease
Masaru Katoh
β‑catenin/CTNNB1 is an intracellular scaffold protein that interacts with adhesion molecules (E‑cadherin/CDH1, N‑cadherin/CDH2, VE‑cadherin/CDH5 and α‑catenins), transmembrane‑type mucins (MUC1/CD227 and MUC16/CA125), signaling regulators (APC, AXIN1, AXIN2 and NHERF1/EBP50) and epigenetic or transcriptional regulators (BCL9, BCL9L, CREBBP/CBP, EP300/p300, FOXM1, MED12, SMARCA4/BRG1 and TCF/LEF). Gain‑of‑function CTTNB1 mutations are detected in bladder cancer, colorectal cancer, gastric cancer, liver cancer, lung cancer, pancreatic cancer, prostate cancer and uterine cancer, whereas loss‑of‑function CTNNB1 mutations are also detected in human cancer...
May 17, 2018: International Journal of Molecular Medicine
Nenggang Zhang, Debananda Pati
Sepin-1, a potent non-competitive inhibitor of separase, inhibits cancer cell growth, but the mechanisms of Sepin-1-mediated growth inhibition are not fully understood. Here we report that Sepin-1 hinders growth of breast cancer cells, cell migration, and wound healing. Inhibition of cell growth induced by Sepin-1 in vitro doesn't appear to be through apoptosis but rather due to growth inhibition. Following Sepin-1 treatment caspases 3 and 7 are not activated and Poly (ADP-ribose) polymerase (Parp) is not cleaved...
2018: Journal of Cancer Science & Therapy
Xiaodong Jiao, Wenlong Yu, Jianxin Qian, Ying Chen, Peilian Wei, Wenzheng Fang, Guanzhen Yu
BACKGROUND: A-disintegrin and metalloproteinases (ADAMs) are members of a family of multidomain transmembrane and secreted proteins. Specific ADAMs are upregulated in human cancers and correlated with tumor progression and poor outcome, but rarely studied in human hilar cholangiocarcinoma (HC). This study aimed to explore the expression profiles of ADAMs and their potential underlying mechanisms promoting cancer progression. METHODS: mRNA expression of ADAM-9, - 10, - 11, - 12, - 15, - 17, - 28, and - 33 was analyzed in human hilar cholangiocarcinoma (HC) samples...
May 18, 2018: BMC Cancer
Satoshi Ogura, Yuichi Yoshida, Tomohide Kurahashi, Mayumi Egawa, Kunimaro Furuta, Shinichi Kiso, Yoshihiro Kamada, Hayato Hikita, Hidetoshi Eguchi, Hisakazu Ogita, Yuichiro Doki, Masaki Mori, Tomohide Tatsumi, Tetsuo Takehara
Dysregulation of cell metabolism is a hallmark of cancer. The mevalonate pathway in lipid metabolism has been implicated as a potential target of cancer therapy for hepatocellular carcinoma (HCC). The role of the Forkhead Box M1 (FoxM1) transcription factor in HCC development has been well documented, however, its involvement in cancer metabolism of HCC has not been fully determined. Here, we hypothesized that FoxM1 is involved in the mevalonate pathway of cholesterol biosynthesis in HCC. Inhibition of the mevalonate pathway by statins, inhibitors of 3-hydroxy-3-methylglutaryl CoA reductase (HMGCR), resulted in reduced expression of FoxM1 and increased cell death in human hepatoma cells...
April 20, 2018: Oncotarget
Sharmistha Pal, David Kozono, Xiaodong Yang, Wojciech Fendler, Whitney Fitts, Jing Ni, John A Alberta, Jean Zhao, Kevin X Liu, Jie Bian, Nathalene Truffaux, William A Weiss, Adam C Resnick, Pratiti Bandopadhayay, Keith L Ligon, Steven G Dubois, Sabine Mueller, Dipanjan Chowdhury, Daphne A Haas-Kogan
Aberrant chromatin remodeling and activation of the phosphatidylinositol 3-kinase (PI3K) pathway have been identified as important mediators of pediatric high-grade glioma (pHGG) and diffuse intrinsic pontine glioma (DIPG) pathogenesis. As inhibition of these pathways are promising therapeutic avenues and radiation is the only modality to prolong survival of DIPG patients, we sought to explore radiosensitizing functions of such inhibition and explore mechanisms of action of such agents. Here we demonstrate that combined treatment with radiotherapy and CUDC-907, a novel first-in-class dual inhibitor of histone deacetylases (HDAC) and PI3K, evokes a potent cytotoxic response in pHGG and DIPG models...
May 14, 2018: Cancer Research
Bowen Yuan, Youhong Liu, Xiaohui Yu, Linglong Yin, Yuchong Peng, Yingxue Gao, Qianling Zhu, Tuoyu Cao, Yinke Yang, Xuegong Fan, Xiong Li
Therapy-induced expansion of cancer stem cells (CSCs) has been identified as one of the most critical factors contributing to therapeutic resistance, but the mechanisms of this adaptation are not fully understood. UHRF1 is a key epigenetic regulator responsible for therapeutic resistance, and controls the self-renewal of stem cells. In the present study, taxane-resistant cancer cells were established and stem-like cancer cells were expanded. UHRF1 was overexpressed in the taxane-resistant cancer cells, which maintained CSC characteristics...
May 11, 2018: Cell Death & Disease
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