Prognostic significance of microRNA-20a-5p levels which promotes proliferation and invasion by targeting cyclin G2 in small cell lung cancer

MicroRNA-20a-5p (miR-20a-5p) has been shown to function as a tumor promoter factor in several cancers. However, its role in small cell lung cancer (SCLC) remains unclear. In this study, we have made an attempt to measure the tumor tissue levels of miR-20a-5p in patients with SCLC using quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). The biological function of miR-20a-5p in SCLC cells was investigated in vitro and in vivo studies, including cell proliferation, migration assays and tumorigenicity in nude mice. Meanwhile?we conducted the luciferase reporter assay to verify the biological relationship between miR-20a-5p and CCNG2. The expression of miR-20a-5p was significantly upregulated in human SCLC compared to that in normal tissues. Kaplan-Meier analysis indicated that patients with high expression of miR-20a-5p are closely related with the shorter survival of SCLC. Further, multivariate analysis showed that miR-20a-5p was an independent prognostic factor. Increasing miR-20a-5p expression promotes the proliferation, migration and invasion of the NCI-H446 cells in vitro and in vivo. Dual-luciferase reporter gene assay demonstrated that miR-20a-5p directly targets CCNG2. These findings suggest that miR-20a-5p levels might be a novel diagnostic and prognostic marker of SCLC. Inhibiting miR-20a-5p could be a promising therapeutic strategy for SCLC.

Role of the bHLH transcription factor TCF21 in development and tumorigenesis

Transcription factors control, coordinate, and separate the functions of distinct network modules spatially and temporally. In this review, we focus on the transcription factor 21 (TCF21) network, a highly conserved basic-helix-loop-helix (bHLH) protein that functions to integrate signals and modulate gene expression. We summarize the molecular and biological properties of TCF21 control with an emphasis on molecular and functional TCF21 interactions. We suggest that these interactions serve to modulate the development of different organs at the transcriptional level to maintain growth homeostasis and to influence cell fate. Importantly, TCF21 expression is epigenetically inactivated in different types of human cancers. The epigenetic modification or activation and/or loss of TCF21 expression results in an imbalance in TCF21 signaling, which may lead to tumor initiation and, most likely, to progression and tumor metastasis. This review focuses on research on the roles of TCF21 in development and tumorigenesis systematically considering the physiological and pathological function of TCF21. In addition, we focus on the main molecular bases of its different roles whose importance should be clarified in future research. For this review, PubMed databases and keywords such as TCF21, POD-1, capsulin, tumors, carcinomas, tumorigenesis, development, and mechanism of action were utilized. Articles were selected within a historical context as were a number of citations from journals with relevant impact.

Cancer stem cells in radiation resistance of esophageal cancer:role and molecular mechanism / 中华放射肿瘤学杂志

Objective To investigate the role of cancer stem cells in radiation resistance of esophageal cancer and its molecular mechanism, and to provide a theoretical basis for radiotherapy for esophageal cancer.Methods Esophageal cancer cell line TE1 was treated with 8 Gy of radiation. Esophageal cancer cell line with resistance to radiation, TE1-res, was established and screened.Cell counting was used to evaluate cell proliferation.Flow cytometry was used to determine the expression of CD44 (high) CD24(-) CD133(+) and apoptosis in cells.The colony formation assay was used to determine the colony-forming rate and cell survival curve.Bisulfite sequencing PCR was used to determine the methylation status of cancer suppressor genes.Comparison of the data was made by group t test or analysis of variance. Results Compared with TE1 cells, TE1-res cells had significantly enhanced proliferation, a significantly higher proportion of CD44( high) CD24(-) CD133(+) cells, and significantly enhanced resistance to apoptosis (mean value 20.84×105 vs.4.46×105/day, P=0.008;(38.0±2.9)%vs.(10.1±1.3)%, P=0.001;mean value 33.23% vs.10.50%, P=0.003 ) .After treatment with 8 Gy of radiation, TE1-res cells had significantly higher colony-forming rate and D0 value than TE1 cells ((14.3±2.6)%vs.(0.9±0.3)%, P=0.011;3.28 vs.2.19 Gy, P=0.125 ) .Moreover, the promoter methylation in cancer suppressor genes including SPINT2, CDKN1B, DKK1, TP53, and PPP2R1B was significantly enhanced in TE1-res cells than in TE1 cells ((89.7±4.9)%vs.(5.0±0.5)%, P=0.001;(92.3±4.7)%vs.(10.4±0.7)%, P=0.001;(90.7±3.7)%vs.(7.9±0.4)%, P=0.001;(83.4±5.7)%vs.(17.2±1.2)%, P=0.002;(90.2± 6.7)%vs.(4.4±1.2)%, P=0.002).Conclusions Cancer stem cells play an important role in radiation resistance of esophageal cancer. The resistance to radiation is closely associated with promoter hypermethylation in cancer suppressor genes including SPINT2, CDKN1B, DKK1, TP53, and PPP2R1B.

Impact of down-regulation of histone methyltransferase enhancer of zeste homolog 2 on RUNX3 expressions, proliferation and apoptosis in human pancreatic cancer / 中华肝胆外科杂志

Objective To investigate the impact of down-regulation of histone methyltransferase enhancer of zeste homolog 2 (EZH2) on RUNX3 expressions,proliferation and apoptosis in human pancreatic cancer.Methods The expressions of EZH2 and RUNX3 in 38 pancreatic cancer patients and human pancreatic cancer AsPC-1,PANC-1 and BxPC-3 cells were detected by immunohistochemistry and western blot,respectively.Cells were transfected with siEZH2 by lipofectamin 2000.Real time-PCR and western blot were used to detect EZH2 and RUNX3 expressions.Cell growth and apoptosis in vitro and vivo were assessed by MTT,flow cytometry and nude mice experiments,respectively.The correlation among the expressions of EZH2,clinical pathological features and overall survival rate were analyzed.Results Elevated EZH2 and decreased RUNX3 expressions were observed in human pancreatic cancer tissues and cells (P ＜ 0.05).Knockdown of EZH2 reduced cell growth and induced apoptosis in vitro and vivo by upregulating RUNX3 protein expression (P ＜ 0.05).In addition,the EZH2 expressions were correlated with tumor stage,lymph node metastasis and poor prognosis (P ＜ 0.05).Conclusions EZH2 expressions were correlated with malignancy and poor prognosis in pancreatic cancer.Tumor cell proliferation was promoted by EZH2 through down-regulation of RUNX3.EZH2 may be a potential therapeutic target for pancreatic cancer.

Research progress on the circadian clock gene PER in tumors / 中国肿瘤临床

Circadian clock governs 24-hour rhythms in body temperature, blood pressure, circulating hormones, metabolism, and oth-er physiological parameters in humans and most mammals. The circadian clock is regulated by circadian clock genes. For instance, peri-od (PER) is a core circadian clock gene. Human PER includes PER1, PER2, and PER3, which play a role in cancer suppression. Abnormal PER expression not only causes cancer but also changes cellular sensitivity to radiation and chemotherapeutic drugs. Thus, this theory has provided a new direction for cancer radiotherapy and chemotherapy. This paper presents the research progress on PER in tumors.

Association of ATBF1 and the growth and progression of malignant tumor / 国际外科学杂志

AT motif binding factor 1 (ATBF1) gene,is a new tumor suppressor gene,and one of its expression variants by alternative splicing,known as ATBF1-A,can bind to the enhancer AT-rich element of alpha fetoprotein (AFP) and down-regulate the transcription of AFP,which may suppress the development and induce the apoptpsis of some carcinoma cells.In this review,we attempted to analysis the pathway of ATBF1 behaves with other factors and its multiple biological functions;ATBF1 function as a suppressor gene,it was illustrated for the influence on the growth and invasion of breast,prostate or gastric cancer.We also discussed the application of the ATBF1 level function as a cancer predictor,and forecasted the significance to apply ATBF1 for the therapy of cancer.

EBP50:a Novel Cancer Suppressor Protein / 生物化学与生物物理进展

EBP50(ERM-binding phosphoprotein-50),a multifunctional adapter protein with 358 amino acids and two PDZ domains, regulates cell growth and migration. Lines of evidences indicate that it is a potential cancer suppressor protein. Loss of heterozygosity (LOH) and intragenic mutation of the ebp50 gene have been found in both primary breast tumors and breast cancer cell lines. EBP50 suppresses the breast cancer cell proliferation via its interaction with many tumor suppressor protein including PTEN, SYK, MERLIN, etc. Here the molecular structure of EBP50, signal pathway regulated by EBP50, and the relationship between breast cancer development and EBP50 are discussed.

Induction of apoptosis in oral cancer cell line through an recombinant HCCS-1 adenovirus

Despite advances in surgery, radiotherapy, and chemotherapy, the survival of patients with oral squamous cell carcinoma has not significantly improved over the past several decades. Gene therapy is currently under investigation and shows us new possibility of cancer curing method. This experiment was undergone to find out the cell growth inhibition effect and evidence of apoptosis by HCCS-1(human cervical cancer suppressor-1), one of the candidates of tumor suppressor gene, transducted to human oral cancer cell line. To determine the efficiency of the adenovirus as a gene delivery vector cell line was transducted with LacZ gene and analysed with X-gal staining. Northern blot was performed to confirm the transfection with HSCC-1 gene and cell viability was assessed by cell cytotoxicity assay using cell count kit(CCK). To show the evidence of apoptosis, DNA fragmentation assay and flow cytometry(FACS) were performed. We had successfully construct the recombinant HSCC-1 adenovirus(Ad5CMV-HCCS-1), and importation efficiency was 20% at 2 MOI(multiplicity of infection), 80% at 20 MOI. Northern blot analysis showed that a single 0.6kb mRNA transcript was expressed in Ad5CMV-HCCS-1 transducted cell lines. As a result of CCK, when comparing to control subjects, transducted group showed 50% growth inhibition. In DNA fragmentation assay, according to increasing of MOI, DNA volume was diminished. In FACS analysis, DNA distribution showed fragmentation.This results imply that HCCS-1gene has growth inhibition effect in human oral cancer cell lines through apoptosis induction.

Recent advance in the regulation of PTEN's function / 中国药理学通报

The tumor suppressor PTEN is a dual-specificity phosphatase possessing both protein phosphatase and lipid phosphatase activity. PTEN inhibits phosphatidylinositol-3-kinase (PI3-K)/ Akt signaling pathway by dephosphorylating phosphatidylinositol-(3,4,5)-triphosphate at the 3 site. PTEN plays a pivotal role in cell growth, proliferation, migration, and apoptosis. The deregulation of PTEN has been implicated in a variety of human cancers such as prostate, endometrial, and breast cancers. Cellular PTEN's function appears to be regulated by its expression, phosphorylation, oxidation, and membrane binding. This review summarized the current progress in the molecular mechanism of PTEN's function.