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1.
FEBS Lett ; 589(6): 702-9, 2015 Mar 12.
Article in English | MEDLINE | ID: mdl-25666710

ABSTRACT

In our study, transcriptome microarrays are used to identify differentially expressed miRNAs and mRNAs in cervical cancer specimens. We find that microRNA-145 (miR-145) expression is significantly decreased in cervical cancer tissues and cell lines, and is associated with advanced cancer stages, large tumor size and moderate/poor differentiation. We show that miR-145 targets the DNA damage repair-associated gene Helicase-like transcription factor (HLTF), which is involved in radio-resistance. Moreover, miR-145 over-expression in cervical cancer cells enhances radiosensitivity in vitro and in vivo. These results indicate that targeting miR-145 may be a novel radiosensitizing strategy for cervical cancer.


Subject(s)
MicroRNAs/physiology , Uterine Cervical Neoplasms/metabolism , Adult , Animals , Base Sequence , Binding Sites , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Female , Gene Expression Regulation, Neoplastic , HeLa Cells , Humans , Mice, Inbred BALB C , Mice, Nude , Middle Aged , Oligonucleotide Array Sequence Analysis , RNA Interference , Radiation Tolerance , Transcription Factors/genetics , Transcription Factors/metabolism , Transcriptome , Tumor Burden/radiation effects , Uterine Cervical Neoplasms/pathology , Uterine Cervical Neoplasms/radiotherapy , Xenograft Model Antitumor Assays
2.
Hepatology ; 60(4): 1278-90, 2014 Oct.
Article in English | MEDLINE | ID: mdl-25043274

ABSTRACT

UNLABELLED: Many protein-coding oncofetal genes are highly expressed in murine and human fetal liver and silenced in adult liver. The protein products of these hepatic oncofetal genes have been used as clinical markers for the recurrence of hepatocellular carcinoma (HCC) and as therapeutic targets for HCC. Herein we examined the expression profiles of long noncoding RNAs (lncRNAs) found in fetal and adult liver in mice. Many fetal hepatic lncRNAs were identified; one of these, lncRNA-mPvt1, is an oncofetal RNA that was found to promote cell proliferation, cell cycling, and the expression of stem cell-like properties of murine cells. Interestingly, we found that human lncRNA-hPVT1 was up-regulated in HCC tissues and that patients with higher lncRNA-hPVT1 expression had a poor clinical prognosis. The protumorigenic effects of lncRNA-hPVT1 on cell proliferation, cell cycling, and stem cell-like properties of HCC cells were confirmed both in vitro and in vivo by gain-of-function and loss-of-function experiments. Moreover, mRNA expression profile data showed that lncRNA-hPVT1 up-regulated a series of cell cycle genes in SMMC-7721 cells. By RNA pulldown and mass spectrum experiments, we identified NOP2 as an RNA-binding protein that binds to lncRNA-hPVT1. We confirmed that lncRNA-hPVT1 up-regulated NOP2 by enhancing the stability of NOP2 proteins and that lncRNA-hPVT1 function depends on the presence of NOP2. CONCLUSION: Our study demonstrates that the expression of many lncRNAs is up-regulated in early liver development and that the fetal liver can be used to search for new diagnostic markers for HCC. LncRNA-hPVT1 promotes cell proliferation, cell cycling, and the acquisition of stem cell-like properties in HCC cells by stabilizing NOP2 protein. Regulation of the lncRNA-hPVT1/NOP2 pathway may have beneficial effects on the treatment of HCC.


Subject(s)
Carcinoma, Hepatocellular/physiopathology , Cell Proliferation/physiology , Liver Neoplasms/physiopathology , Neoplastic Stem Cells/physiology , Nuclear Proteins/physiology , RNA, Long Noncoding/physiology , tRNA Methyltransferases/physiology , Animals , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/pathology , Cell Cycle/physiology , Disease Models, Animal , Female , Humans , In Vitro Techniques , Liver Neoplasms/mortality , Liver Neoplasms/pathology , Male , Mice , Middle Aged , Phenotype , Prognosis , Signal Transduction/physiology , Transforming Growth Factor beta1/physiology
3.
PLoS One ; 9(7): e100340, 2014.
Article in English | MEDLINE | ID: mdl-25007342

ABSTRACT

In recent years, long noncoding RNAs (lncRNAs) have been demonstrated to play key roles in tumorgenesis. However, the contributions of lncRNAs to cervical cancer (CC) remain largely unknown. In this study, differentially expressed lncRNAs and mRNAs in cervical cancer and paired peritumoral tissues were detected by transcriptome microarray analysis. We found 708 probe sets of lncRNAs increased and 836 probe sets decreased in CC tissues, while 1288 mRNA differential probe sets increased and 901 mRNA probe sets decreased. The results were validated by quantitative real-time polymerase chain reaction (qPCR). Then, we found a specific differentially expressed lncRNA can physically bind to enhancer of zeste homolog2 (EZH2) by using RNA immunoprecipitation. We termed it as EZH2-binding lncRNA in cervical cancer [lncRNA-EBIC]. Wound healing assays and Matrigel invasion assays were used to determine the function of this lncRNA by silencing it. We observed that the migration and invasion of cervical cancer cells in vitro were inhibited upon suppression of lncRNA-EBIC by siRNA. We also found that the association between lncRNA-EBIC and EZH2 was required for the repression of E-cadherin, which was a key molecular in the metastasis of cervical cancer. Conclusion: These results demonstrated that lncRNA-EBIC was an oncogenic lncRNA, which could promote tumor cell invasion in CC by binding to EZH2 and inhibiting E-cadherin expression.


Subject(s)
Cadherins/genetics , Gene Expression Regulation, Neoplastic , Polycomb Repressive Complex 2/metabolism , RNA, Long Noncoding/physiology , Uterine Cervical Neoplasms/metabolism , Antigens, CD , Cadherins/metabolism , Cell Movement , Enhancer of Zeste Homolog 2 Protein , Female , HeLa Cells , Humans , Neoplasm Invasiveness , Transcriptome , Uterine Cervical Neoplasms/genetics , Uterine Cervical Neoplasms/pathology
4.
Cancer Cell ; 25(5): 666-81, 2014 May 12.
Article in English | MEDLINE | ID: mdl-24768205

ABSTRACT

The role of TGF-ß-induced epithelial-mesenchymal transition (EMT) in cancer cell dissemination is well established, but the involvement of lncRNAs in TGF-ß signaling is still unknown. In this study, we observed that the lncRNA-activated by TGF-ß (lncRNA-ATB) was upregulated in hepatocellular carcinoma (HCC) metastases and associated with poor prognosis. lncRNA-ATB upregulated ZEB1 and ZEB2 by competitively binding the miR-200 family and then induced EMT and invasion. In addition, lncRNA-ATB promoted organ colonization of disseminated tumor cells by binding IL-11 mRNA, autocrine induction of IL-11, and triggering STAT3 signaling. Globally, lncRNA-ATB promotes the invasion-metastasis cascade. Thus, these findings suggest that lncRNA-ATB, a mediator of TGF-ß signaling, could predispose HCC patients to metastases and may serve as a potential target for antimetastatic therapies.


Subject(s)
Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/genetics , Liver Neoplasms/pathology , RNA, Long Noncoding/genetics , Transforming Growth Factor beta/metabolism , Animals , Epithelial-Mesenchymal Transition/genetics , Gene Expression Profiling , Homeodomain Proteins/biosynthesis , Homeodomain Proteins/metabolism , Humans , Interleukin-11/genetics , Male , Mice , Mice, Inbred BALB C , Mice, Nude , MicroRNAs/metabolism , Neoplasm Invasiveness , Neoplasm Metastasis , Neoplasm Transplantation , Prognosis , RNA, Messenger/metabolism , Repressor Proteins/biosynthesis , Repressor Proteins/metabolism , STAT3 Transcription Factor/metabolism , Transcription Factors/biosynthesis , Transcription Factors/metabolism , Transplantation, Heterologous , Tumor Cells, Cultured , Up-Regulation , Zinc Finger E-box Binding Homeobox 2 , Zinc Finger E-box-Binding Homeobox 1
5.
Huan Jing Ke Xue ; 33(6): 1808-15, 2012 Jun.
Article in Chinese | MEDLINE | ID: mdl-22946159

ABSTRACT

In order to investigate the heavy metal concentrations and their potential ecological risks in surface sediments of lower reaches and estuary of Pearl River, 21 bottom sediment samples were collected from lower reaches and estuary of Pearl River. Total contents of Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Se, Cd, Sb, Pb and Hg in these samples were measured by the inductively coupled plasma mass spectrometry (ICP-MS) and the atomic fluorescence spectrometry (AFS) and using the index of geoaccumulation and the potential ecological risk index to evaluate the pollution degree of heavy metals in the sediments. Results indicated that the concentration of total Fe and total Mn were 41658.73 and 1104.73 mg x kg(-1) respectively and toxic trace metals, such as Cr, Co, Ni, Cu, Zn, As, Se, Cd, Sb, Pb and Hg were 86.62, 18.18, 54.10, 80.20, 543.60, 119.55, 4.28, 10.60, 20.26, 104.58 and 0.520 mg x kg(-1). The descending order of pollution degree of various metals is: Cd > As approximately Zn > Hg > Pb approximately Cu approximately Cr, while the single potential ecological risk followed the order: Cd > Hg > As > Cu > Pb > Zn > Cr. The pollution extent and potential ecological risk of Cd were the most serious among all heavy metals. The distribution pattern of Cd individual potential ecological risk indices is exactly the same as that of general potential ecological risk indices for all heavy metals. Clustering analysis indicates that the sampling stations may be classified into five groups which basically reflected the characteristics of the heavy metal contamination and sedimentation environments along the different river reaches in lower reaches and estuary of Pearl Rive. In general, the serious heavy metal pollution and the high potential ecological risk existed in three river reaches: Chengcun-Shawan, Chengcun-Shundegang and Waihai-Hutiaomen. The pollution degree and potential ecological risk are higher in related river reaches of Beijiang than that in other lower reaches and estuary of Pearl River.


Subject(s)
Geologic Sediments/analysis , Metals, Heavy/analysis , Water Pollutants, Chemical/analysis , China , Cluster Analysis , Ecological and Environmental Phenomena , Environmental Monitoring , Risk Assessment , Rivers
6.
Yi Chuan ; 31(3): 245-54, 2009 Mar.
Article in Chinese | MEDLINE | ID: mdl-19273436

ABSTRACT

BMPs belong to the transforming growth factor-b superfamily. BMPs have been proved to have extensive biological functions in mammals, including growth regulation, cell proliferation and differentiation. More and more evidence has shown that BMPs play a key role in fertility, especially in folliculogenesis in female mammals. Smad proteins are intra-cellular signaling transduction molecules of BMP family, which can transduce the BMP signal from the cell membrane to the nucleus. In this review, BMPs, BMP/Smad-related signal transduction and the regulation of BMP activity were summarized, and the regulatory roles of BMP/Smad signal transduction pathway in folliculogenesis were discussed.


Subject(s)
Bone Morphogenetic Proteins/physiology , Ovarian Follicle/physiology , Signal Transduction/physiology , Smad Proteins/physiology , Animals , Bone Morphogenetic Proteins/genetics , Bone Morphogenetic Proteins/metabolism , Cell Differentiation/genetics , Cell Differentiation/physiology , Female , Humans , Ovarian Follicle/cytology , Signal Transduction/genetics , Smad Proteins/genetics , Smad Proteins/metabolism
7.
Sheng Wu Gong Cheng Xue Bao ; 22(5): 845-9, 2006 Sep.
Article in Chinese | MEDLINE | ID: mdl-17037213

ABSTRACT

291 embryos (Blastocyst/Morula) from 20 donor sows were vitrified by two step method with OPS (open pulled straw) in solution I (TCM199 + 20% FBS + 10% EG + 10% DMSO) for 3min, and solution II (TCM199 + 20% FBS + 20% EG + 20% DMSO + 0.4mol/L SUC) for 1min, stored in liquid nitrogen for 3 months, and transferred into 8 recipient sows after warming, one recipient sow was pregnant and 8 alive piglets were born. This is the first paper to report getting alive piglets by vitrification in China.


Subject(s)
Blastocyst/physiology , Cryopreservation/methods , Cryopreservation/veterinary , Swine/embryology , Animals , Embryo Transfer , Female , Pregnancy
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