Cancer Biomarkers - Volume 23, issue 4

Authors: Qin, Jun | Bao, Hongxia | Li, Hong

Article Type: Research Article

Abstract: OBJECTIVE: This study aimed to investigate the correlation of long non-coding RNA taurine-upregulated gene 1 (lncRNA TUG1) with clinicopathological characteristics and prognosis in acute myeloid leukemia (AML) patients, as well as its function in cell proliferation and apoptosis. METHODS: Two hundred and thirty six de novo AML patients were consecutively enrolled and then underwent conventional induction chemotherapy. Bone marrow samples were obtained from all AML patients and controls. Quantitative polymerase chain reaction assay was performed to detect lncRNA TUG1 expression. KG-1 cells were transfected by TUG1 inhibitor (TUG1 (- )) and blank inhibitor …(NC (- )) plasmids. Cell proliferation and apoptosis were evaluated by CCK8 and AV/PI assays, and apoptotic markers expressions were detected by Western blot assay. RESULTS: LncRNA TUG1 expression was higher in AML patients compared to controls, and it was positively correlated with white blood cell counts as well as poor risk stratification. Additionally, elevated lncRNA TUG1 expression was observed in non-complete remission (non-CR) patients compared to CR patients, and it was correlated with shorter event-free survival and overall survival in AML patients. In the in vitro experiments, lncRNA TUG1 expression was upregulated in AML cell lines compared to control cells, and cell proliferation ability was reduced, but cell apoptosis rate was promoted in TUG1 (- ) group compared to NC (- ) group at 72 hours after transfection in KG-1 cells. CONCLUSIONS: LncRNA TUG1 predicts advanced disease conditions and poor prognosis in AML patients, and its knockout decreases proliferation and increases apoptosis of AML cells. Show more

Keywords: Taurine-upregulated gene 1 (TUG1), acute myeloid leukemia (AML), prognosis, proliferation, apoptosis

DOI: 10.3233/CBM-181834

Citation: Cancer Biomarkers, vol. 23, no. 4, pp. 569-577, 2018

Authors: Zhuo, Xianlu | Zhou, Wei | Li, Dairong | Chang, Aoshuang | Wang, Ying | Wu, Yongzhong | Zhou, Qi

Article Type: Research Article

Abstract: BACKGROUND: Increasing studies have identified a series of circulating mircoRNAs (miRNAs) as biomarkers for disease detection due to their stability in the blood. The aim of the present study was to identify specific plasma miRNAs as potential biomarkers for nasopharyngeal carcinoma (NPC) detection. MATERIALS AND METHODS: Relative public microarray data were obtained and analyzed for screening of the plasma differentially expressed miRNAs (DEMs) between NPC patients and controls. This study contained two phases: a screening phase and a validation one. Logistic regression and receiver operating characteristics curve (ROC) analyses were used to identify DEM signatures. Moreover, …targeted genes of the selected DEMs were predicted and their functions were annotated by using bioinformatic analysis. RESULTS: Both the screening and the validation phases showed that three miRNAs (miR-548q, miR-630 and miR-940) in the plasma of NPC patients were up-regulated compared to those of controls. They can be used as biomarkers for discriminating NPC patients from non-cancerous controls. Moreover, we found a classifier including only two miRNAs (miR-548q and miR-940) that can be used as a diagnostic signature for NPC, achieving an area under curve (AUC) of 0.972, a sensitivity of 0.94, and a specificity of 0.925. CONCLUSIONS: The present study demonstrated that three miRNAs (miR-548q, miR-630 and miR940) might be novel and useful biomarkers for NPC detection. A two-miRNA signature (miR-548q and miR940) may be considered as a better biomarker for NPC detection with relatively high sensitivity and specificity. Future studies with large sample sizes are needed for further validation. Show more

Keywords: Nasopharyngeal carcinoma, diagnosis, microRNA, accuracy, plasma

DOI: 10.3233/CBM-181852

Citation: Cancer Biomarkers, vol. 23, no. 4, pp. 579-587, 2018

Authors: Yang, Wei | Shan, Zhiming | Zhou, Xinfang | Peng, Liangqun | Zhi, Chongyang | Chai, Junhui | Liu, Hongxing | Yang, Junmei | Zhang, Zhandong

Article Type: Research Article

Abstract: OBJECTIVE: Osteosarcoma is the most common primary malignant skeleton tumor that derives from mesenchymal cells. Emerging evidences have identified the vital role of long non-coding RNAs (lncRNAs) in the development of osteosarcoma. In this study, we aimed to investigate the role of lncRNA gastric carcinoma highly expressed transcript 1 (GHET1) in osteosarcoma progression. METHODS: The expression levels of relevant genes in clinical samples and cell lines were determined by quantitative real-time PCR. Cell proliferation was determined by CCK8 and cell colony formation assays. Transwell assay was used to detect the invasion and migration of osteosarcoma cells. …Cell apoptosis and cell cycle were detected by flow cytometry. Protein levels were detected by western blot. In vivo tumor growth was investigated in the xenograft nude mice model. To determine whether growth inhibition and apoptosis are responsible for antitumor activity of silencing GHET1, immunohistochemistry for proliferation and TUNEL assay was performed in xenograft tissues. In vivo lung metastasis was performed to detect the effect of GHET1 on cell metastasis ability. RESULTS: Our results revealed that GHET1 was up-regulated in osteosarcoma tissues compared to normal tissues. GHET1 was also increased in osteosarcoma cell lines compared to normal osteoplastic cell line. The up-regulation of GHET1 was significantly associated with TNM stage, distant metastasis and lymph node metastasis in patients with osteosarcoma. In vitro studies showed that silencing GHET1 in MG-63 and U2OS cells inhibited cell proliferation, cell invasion and migration and epithelial-to-mesenchymal transition (EMT), promoted cell apoptotic rate, and also caused an increase in cell population at G 0 /G 1 phase with a decrease in cell population at S phase. Overexpression of GHET1 promoted the proliferation, invasion and migration of osteosarcoma cells. Importantly, silencing GHET1 inhibited tumor growth and tumor metastasis in mice MG-63-xenograft model in association with changes of EMT-related genes, reduced expression of Ki-67 and promotion of apoptosis. CONCLUSION: GHET1 was up-regulated in osteosarcoma tissues and cell lines, inhibited cell apoptosis, promoted cell proliferation, invasion and migration by affecting EMT in vitro , and was correlated with the tumor growth and metastasis in vivo . GHET1 may be a potential therapeutic target of osteosarcoma treatment. Show more

Keywords: Osteosarcoma, GHET1, metastasis, cell proliferation, invasion and migration

DOI: 10.3233/CBM-181863

Citation: Cancer Biomarkers, vol. 23, no. 4, pp. 589-601, 2018

Authors: Liu, Zhi-Biao | Tang, Chen | Jin, Xin | Liu, Shou-Hou | Pi, Wen

Article Type: Research Article

Abstract: BACKGROUND: Small nucleolar RNA host gene 12 (SNHG12) has been shown to be a long noncoding RNA (lncRNA) that facilitates the progression of a number of malignancies. However, the expression pattern and biological function of SNHG12 in nasopharyngeal carcinoma (NPC) have not been investigated. OBJECTIVE: The aim of our study is to investigate the expression, clinical significance and function of SNHG12 in NPC. METHODS: RT-PCR was used to detect the expression of SNHG12 in NPC cell lines and primary tumor tissues. The correlation of SNHG12 with clinicopathological features and patient prognosis was analyzed. …The biologic functions of SNHG12 in NPC were explored by MTT assay, colony formation assay, wound healing assays, transwell assay and flow cytometric analysis in vitro . The expression of EMT markers and Notch signal pathway markers were determined by western blotting. RESULTS: The expression levels of SNHG12 were up-regulated in both NPC tissues and cell lines. High SNHG12 expression was significantly associated with clinical stage, grade and poor prognosis. Multivariate analysis demonstrated that high lncRNA SNHG12 expression was an independent poor prognostic factor for NPC patients. Functionally, knockdown of SNHG12 suppressed NPC cells proliferation, migration and invasion. Mechanistic investigations showed that knockdown of SNHG12 suppressed the activation of EMT and Notch-1 signal pathway. CONCLUSIONS: Our data suggest that SNHG12 promotes the progression of NPC and is a potential therapeutic target for NPC intervention. Show more

Keywords: LncRNA, SNHG12, nasopharyngeal carcinoma, prognosis, Notch-1 signal pathway, metastasis

DOI: 10.3233/CBM-181873

Citation: Cancer Biomarkers, vol. 23, no. 4, pp. 603-613, 2018