Abstract:
:MicroRNA-153 (miR-153) is considered to be a tumor regulator. Silencing of miR-153 expression induced apoptosis in breast cancer cells. Data on mechanism suggest that up-regulation of miR- 153 level promotes cell proliferation via the down regulation of the expression of PTEN or FOXO1, which attenuates the proliferation of cancerous cells. This study aims to identify the effect of miR-153 on the activity of chemotherapeutic and targeted agents in HCC cells and to investigate the mechanisms involved. MTT, soft agar, trans-well and flow cytometry assays were performed to examine whether miR-153 down-regulated the activity of the chemotherapeutic and targeted drugs, Sorafenib, Etoposide and Paclitaxel in HCC cells. The rate of proliferation inhibition, relative survival rates and IC50 values of each drug were calculated. Western blot and luciferase assays were performed to assess whether miR-153 modulates the expression of important genes related to cell proliferation, apoptosis or survival. Results showed that miR-153 attenuated the effect of Etoposide, Paclitaxel and Sorafenib on HepG2 cells; the IC50 value increased from 0.25±0.01μmol/L to 1.02±0.14μmol/L, 0.05±0.01μmol/L to 0.14±0.02μmol/L and from 1.09±0.15μmol/L to 5.18±0.99μmol/L, respectively. In addition, miR-153 also reduced the effect of these drugs on MHCC- 97H, MHCC-97 L and L-02 cells; and it also reduced the effects of Sorafenib, Etoposide and Paclitaxel on anchor-independent growth of HepG2 cells. Over-expression of miR-153 down-regulated the activity of Etoposide and Paclitaxel on cell cycle arrest of HepG2 cells and the effect of Sorafenib on the invasion and migration of HepG2 cells. Furthermore, overexpression of miR-153 also enhanced the growth of HepG2, MHCC-97H, MHCC-97 L and L-02 cells. Mechanisms data showed that overexpression of miR-153 down regulated the activity of luciferase reporters, p15-Luc and p21-Luc; and enhanced the protein level of pro-survival or anti-apoptosis proteins Survivin and BCL-2. These results show that overexpression of miR-153 protects HepG2 cells against the effects of these drugs via multiple mechanisms, and miR-153 may be a novel target for HCC in future diagnostic and therapeutic interventions.
journal_name
Curr Cancer Drug Targetsjournal_title
Current cancer drug targetsauthors
Chen Y,Feng F,Gao X,Wang C,Sun H,Zhang C,Zeng Z,Lu Y,An L,Qu J,Wang F,Yang Ydoi
10.2174/1568009615666150225122635subject
Has Abstractpub_date
2015-01-01 00:00:00pages
176-87issue
3eissn
1568-0096issn
1873-5576pii
CCDT-EPUB-65443journal_volume
15pub_type
杂志文章abstract::The treatment of advanced non � small cell lung cancer (NSCLC) increasingly involves the use of molecularly targeted therapy with activity against either the tumor directly, or indirectly, through activity against host-derived mechanisms of tumor support such as angiogenesis. The most well studied signaling pathway as...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800912799095144
更新日期:2012-02-01 00:00:00
abstract::Aurora kinases and cyclin-dependent kinases, which play critical roles in the cell cycle and are frequently overexpressed in a variety of tumors, have been suggested as attractive targets for cancer therapy. JNJ-7706621, a recently identified dual inhibitor of these kinases, is reported to induce cell cycle arrest, en...
journal_title:Current cancer drug targets
pub_type: 杂志文章
doi:10.2174/156800912801784839
更新日期:2012-07-01 00:00:00
abstract::The genomic characterization of acute myeloid leukemia (AML) by DNA sequencing has illuminated subclasses of the disease, with distinct driver mutations, that might be responsive to targeted therapies. Approximately 15-23% of AML genomes harbor mutations in one of two isoforms of isocitrate dehydrogenase (IDH1 or IDH2...
journal_title:Current cancer drug targets
pub_type: 杂志文章
doi:10.2174/1568009620666200424145622
更新日期:2020-01-01 00:00:00
abstract::The anticancer properties of histone deacetylase inhibitors have been known for some time. However, it is only recently that the functional identities of the intracellular targets mediating the anticancer properties have started to be revealed. These targets appear to play significant roles in cell cycle control, apop...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009023333818
更新日期:2002-12-01 00:00:00
abstract::Inactivation of the FHIT and TP53 genes is frequently observed in primary non-small cell lung cancers (NSCLC) and cell lines and may contribute to resistance to apoptotic stimuli elicited by various anti-tumor drugs. To evaluate a possible relationship between FHIT and TP53 status and response to platinum-analogue reg...
journal_title:Current cancer drug targets
pub_type: 杂志文章
doi:10.2174/156800908785133204
更新日期:2008-08-01 00:00:00
abstract::Anti-angiogenesis therapy is one major approach of cancer therapies nowadays. Unfortunately, anti-angiogenesis therapy targeting VEGF-A was recently stumbled by the drugresistance that results from adaptive mechanisms, such as intratumor hypoxia. To obtain a more efficient therapeutic response, we created and identifi...
journal_title:Current cancer drug targets
pub_type: 杂志文章
doi:10.2174/156800961603160206125352
更新日期:2016-01-01 00:00:00
abstract::Several subtypes of T cells are located in a tumor environment, each of which supplies their energy using different metabolic mechanisms. Since the cancer cells require high levels of glucose, the conditions of food poverty in the tumor environment can cause inactivation of immune cells, especially the T-effector cell...
journal_title:Current cancer drug targets
pub_type: 杂志文章
doi:10.2174/1568009620666200720010647
更新日期:2020-01-01 00:00:00
abstract::The experimental cytotoxic drug cyclopentenyl cytosine (CPEC) is an analogue of cytidine. Besides its antiviral effect, its potential use in the treatment of cancer has become an important area of research. CPEC is activated by intracellular phosphorylation ultimately forming its metabolite CPEC-TP. CPEC-TP is a non c...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800907781386579
更新日期:2007-08-01 00:00:00
abstract::Exosomes are small vesicles that are secreted by various types of cells, known to mediate signal transduction between cells. During recent years, novel carriers for the delivery of targeted drugs, chemotherapy drugs and RNAs are under development, which is believed to be beneficial for patients. Considering issues of ...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009617666170710120311
更新日期:2018-01-01 00:00:00
abstract::Malignant brain tumors including primary brain tumors (e.g., glioblastoma multiforme) and metastases, are aggressive and lethal entities for the majority of affected patients. Current standard treatments involving combinations of surgery, radiotherapy and systemic chemotherapy offer only modest improvements in surviva...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009615666150616123548
更新日期:2015-01-01 00:00:00
abstract::Polyisoprenylated proteins (PPs) methylation by polyisoprenylated protein methyl transferase (PPMTase) is counteracted by polyisoprenylated methylated protein methyl esterase (PMPMEase). This is the only reversible step of the polyisoprenylation pathway as the relative amounts of the acid and ester forms are determine...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800910791859443
更新日期:2010-09-01 00:00:00
abstract::Prostate cancer is the most frequently diagnosed tumor in industrialized countries. Endocrine therapy, which is based on interference with androgen signaling is only palliative. Drugs used in prostate cancer therapy are luteinizing hormone releasing hormone (LHRH) agonists and antiandrogens. Application of LHRH agonis...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009043332925
更新日期:2004-08-01 00:00:00
abstract::Haem oxygenase-1 (HO-1) catalyses the rate-limiting step in haem degradation. All three metabolites resulting from haem degradation (carbon monoxide (CO), biliverdin and free iron) have anti-inflammatory and anti-apoptotic properties. HO-1 is a stress-inducible enzyme found extensively expressed in a vast variety of b...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009614666140320111306
更新日期:2014-01-01 00:00:00
abstract::UDP-N-acetyl-D-galactosamine: polypeptide N-acetylgalactosaminyl transferase-6 (pp-GalNAc-T6) is a member of the N-acetyl-D-galactosamine transferase family. It catalyzes the addition of N-acetyl-D-galactosamine to proteins, often the first step in O-glycosylation of proteins. Glycosylated proteins play important role...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009616666160922102641
更新日期:2017-01-01 00:00:00
abstract::The evolution of genomic research enabled the genetic and molecular profiling of breast cancer and revealed the profound complexity and heterogeneity of this disease. Subtypes of breast cancer characterized by mutations and/or amplifications of some proto-oncogenes are associated with an increased rate of recurrence a...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009616666160603123014
更新日期:2017-01-01 00:00:00
abstract::Cancer is a disease in which cellular growth regulatory networks are disrupted. Lesions in well-characterized oncogenes and tumor suppressors often contribute to the dysregulation, but recent work has also uncovered the fundamental importance of enzymes that modulate the acetylation status of chromatin to the initiati...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009033481994
更新日期:2003-06-01 00:00:00
abstract::Following the discovery that defective retinoid signaling directly contributes to tumorigenesis, and, that retinoids have an anti-cancer effect in vitro and in vivo, retinoids have become part of the routine care in children with neuroblastoma at the stage of minimal residual disease. However, many patients still rela...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800911796798968
更新日期:2011-09-01 00:00:00
abstract::Membranous Met is classically identified with its role in cancer metastases, while nuclear Met is associated with a more invasive, aggressive and proliferative form of cancer. Full-length Met or N-terminal transmembrane domain cleaved Met can translocate into nucleus in a cell growth and pH dependent but both ligand-d...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009616666160105105250
更新日期:2016-01-01 00:00:00
abstract::Targets for cancer therapy are conventionally selected by identification of molecules acting downstream of established tumour suppressors and oncoproteins, such as p53, c-Myc and Ras. However, the forward genetics approach provides an alternative, conceptually distinct, strategy for identifying target molecules de nov...
journal_title:Current cancer drug targets
pub_type: 杂志文章
doi:
更新日期:2013-01-01 00:00:00
abstract::Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal disorders of hematopoietic progenitors manifest by cytopenias, bleeding, infection, and potential for progression to acute myelogenous leukemia. The wide spectrum of clinical manifestations, including variability in illness severity and potential for ...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800907781662284
更新日期:2007-09-01 00:00:00
abstract::Bisphosphonates are the standard of care for preventing skeletal morbidity and treating hypercalcemia of malignancy in patients with bone metastases. Zoledronic acid (intravenous; 4 mg monthly) is approved to prevent skeletal-related events (SREs) in patients with bone metastases from several tumor types, and can impr...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800909789760267
更新日期:2009-11-01 00:00:00
abstract::Histone deacetylase inhibitors (HDACi) belong to a novel class of drugs able to act on the epigenome, indirectly remodeling the spatial conformation of the chromatin: by increasing histone acetylation these drugs ultimately promote the detachment of the DNA from the nucleosome octamer, therefore allowing the access of...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800908784533508
更新日期:2008-06-01 00:00:00
abstract::Gastrointestinal (GI) tumors are among the leading cause of death in cancer patients worldwide. Particularly, gastric cancer (GC) is the third cause of cancer deaths, whereas esophageal neoplasm is the eighth leading most common cancer worldwide and its incidence, especially adenocarcinoma type, is continuously increa...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009617666170208162058
更新日期:2018-01-01 00:00:00
abstract::Aberrant expression of the RON receptor tyrosine kinase contributes to breast cancer malignancy. Although clinical trials of RON targeting are underway, the intriguing issue is the diversity of RON expression as evident by cancer cells expressing different variants including oncogenic RON160. The current study determi...
journal_title:Current cancer drug targets
pub_type: 杂志文章
doi:10.2174/15680096113139990038
更新日期:2013-07-01 00:00:00
abstract::The integrin family of cell surface receptors integrates cell-extracellular matrix interactions with the cell cytoskeleton and signalling across the cell membrane, resulting in an important role in cell adhesion, mobility and migration, proliferation, and survival. Changes in the number and identity of integrin recept...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800909788486713
更新日期:2009-06-01 00:00:00
abstract::Polysialic acid (polySia) is a carbohydrate polymer critical for neuronal cell migration and axon pathfinding in embryonic development. Besides brain regions requiring persistent neuronal plasticity, polySia is essentially absent from the adult body. However, polySia is aberrantly re-expressed on many tumours, where i...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800912803251225
更新日期:2012-10-01 00:00:00
abstract::Angiogenesis is crucial for tumor development and progression, and antiangiogenetic therapy represents a promising approach for cancer treatment. Thus, the in-depth understanding of the molecular mechanism(s) regulating angiogenesis, together with the characterization of molecules expressed by endothelial cells and in...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009033481741
更新日期:2003-12-01 00:00:00
abstract::Epithelial-mesenchymal transition (EMT) is a developmental process that converts epithelial cells into migratory and invasive cells. This process also plays an important role in cancer progression and metastasis by enabling tumor cells to leave primary sites. EMT is regulated by complex transcription networks and post...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/15680096113136660098
更新日期:2013-11-01 00:00:00
abstract::The resistance of tumors to a number of structurally and functionally unrelated chemotherapeutic drugs has been a major obstacle for successful cancer chemotherapy. An important mechanism leading to multidrug resistance (MDR) is the overexpression of the 170 kDa P-glycoprotein (P-gp), which is a member of the ATP-bind...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/15680096113139990082
更新日期:2013-10-01 00:00:00
abstract::Malignant gliomas are frequently chemoresistant and this resistance seems to depend on at least two mechanisms. First, the poor penetration of many anticancer drugs across the blood-brain barrier (BBB), the blood-cerebrospinal fluid barrier (BCSFB) and blood-tumor barrier (BTB), due to their interaction with several A...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800906777723930
更新日期:2006-08-01 00:00:00