Downregulation of miR-133a-3p promotes prostate cancer bone metastasis via activating PI3K/AKT signaling.

Abstract:

BACKGROUND:Bone metastasis is a leading cause of morbidity and mortality in advanced prostate cancer (PCa). Downexpression of miR-133a-3p has been found to contribute to the progression, recurrence and distant metastasis in PCa. However, clinical significance of miR-133a-3p in bone metastasis of PCa, and the biological role of miR-133a-3p and its molecular mechanisms underlying bone metastasis of PCa remain unclear. METHODS:miR-133a-3p expression was evaluated in 245 clinical PCa tissues by real-time PCR. Statistical analysis was performed to evaluate the clinical correlation between miR-133a-3p expression and clinicopathological features, and overall and bone metastasis-free survival in PCa patients. The biological roles of miR-133a-3p in the bone metastasis of PCa were investigated both in vitro and in vivo. Bioinformatics analysis, real-time PCR, western blot and luciferase reporter analysis were applied to demonstrate the relationship between miR-133a-3p and its potential targets. Western blotting and luciferase assays were examined to identify the underlying pathway involved in the anti-tumor role of miR-133a-3p. Clinical correlation of miR-133a-3p with its targets was verified in human PCa tissues. RESULTS:miR-133a-3p expression is reduced in PCa tissues compared with the adjacent normal tissues and benign prostate lesion tissues, particularly in bone metastatic PCa tissues. Low expression of miR-133a-3p is significantly correlated with advanced clinicopathological characteristics and shorter bone metastasis-free survival in PCa patients by statistical analysis. Moreover, upregulating miR-133a-3p inhibits cancer stem cell-like phenotypes in vitro and in vivo, as well as attenuates anoikis resistance in vitro in PCa cells. Importantly, administration of agomir-133a-3p greatly suppresses the incidence of PCa bone metastasis in vivo. Our results further demonstrate that miR-133a-3p suppresses bone metastasis of PCa via inhibiting PI3K/AKT signaling by directly targeting multiple cytokine receptors, including EGFR, FGFR1, IGF1R and MET. The negative clinical correlation of miR-133a-3p with EGFR, FGFR1, IGF1R, MET and PI3K/AKT signaling activity is determined in clinical PCa tissues. CONCLUSION:Our results unveil a novel mechanism by which miR-133a-3p inhibits bone metastasis of PCa, providing the evidence that miR-133a-3p may serve as a potential bone metastasis marker in PCa, and delivery of agomir-133a-3p may be an effective anti-bone metastasis therapeutic strategy in PCa.

journal_name

J Exp Clin Cancer Res

authors

Tang Y,Pan J,Huang S,Peng X,Zou X,Luo Y,Ren D,Zhang X,Li R,He P,Wa Q

doi

10.1186/s13046-018-0813-4

subject

Has Abstract

pub_date

2018-07-18 00:00:00

pages

160

issue

1

eissn

0392-9078

issn

1756-9966

pii

10.1186/s13046-018-0813-4

journal_volume

37

pub_type

杂志文章
  • Breast cancer and distress resulting from Magnetic Resonance Imaging (MRI): the impact of a psychological intervention of emotional and informative support.

    abstract::The present study assesses the adaptation of a group of female patients with either manifest or suspected breast cancer who have undergone Magnetic Resonance Imaging (MRI) after receiving psychological support. Several studies in literature have reported the effectiveness of such support in reducing anti-oxidant and d...

    journal_title:Journal of experimental & clinical cancer research : CR

    pub_type: 杂志文章

    doi:

    authors: Caruso A,Bongiorno L,Vallini L,Russo P,Tomao F,Grandinetti ML

    更新日期:2006-12-01 00:00:00

  • CDK4 IVS4-nt40 AA genotype and obesity-associated tumors/cancer in Italians - a case-control study.

    abstract:BACKGROUND:Cell cycle checkpoint regulation is crucial for prevention of tumor in mammalian cells. Cyclin-dependant kinase 4 (CDK4) is important in cell cycle regulation, as it controls the G1-S phase of the cell cycle. CDK4 has potential mitogenic properties through phosphorylation of target proteins. We aimed at iden...

    journal_title:Journal of experimental & clinical cancer research : CR

    pub_type: 杂志文章

    doi:10.1186/1756-9966-28-42

    authors: Meenakshisundaram R,Gragnoli C

    更新日期:2009-03-28 00:00:00

  • Oncolytic tanapoxvirus expressing FliC causes regression of human colorectal cancer xenografts in nude mice.

    abstract::Colorectal cancers are significant causes of morbidity and mortality and existing therapies often perform poorly for individuals afflicted with advanced disease. Oncolytic virotherapy is an emerging therapeutic modality with great promise for addressing this medical need. Herein we describe the in vivo testing of reco...

    journal_title:Journal of experimental & clinical cancer research : CR

    pub_type: 杂志文章

    doi:10.1186/s13046-015-0131-z

    authors: Conrad SJ,El-Aswad M,Kurban E,Jeng D,Tripp BC,Nutting C,Eversole R,Mackenzie C,Essani K

    更新日期:2015-02-19 00:00:00

  • Modulation of tumor induced angiogenesis in Ehrlich ascites tumor.

    abstract::In this study the enzyme glutaminase, purified from the ascites fluid of ovarian cancer patients, was analysed for its antiangiogenic activity. Intraperitoneal administration of this enzyme reduces the number of tumor directed capillaries in solid and ascites tumor bearing Swiss mice induced by transplantation of Ehrl...

    journal_title:Journal of experimental & clinical cancer research : CR

    pub_type: 杂志文章

    doi:

    authors: Ghosh S,Roy S,Banerjee M,Maity P

    更新日期:2004-12-01 00:00:00

  • Clinical significance of EGFR, Her-2 and EGF in oral squamous cell carcinoma: a case control study.

    abstract:BACKGROUND:The erbB receptors and their ligands are involved in the pathogenesis and progression of oral squamous cell carcinoma (OSCC). Although EGFR and Her-2 are frequently overexpressed in OSCC, few studies evaluated these proteins in saliva and their association with the tumor, which may represent potential useful...

    journal_title:Journal of experimental & clinical cancer research : CR

    pub_type: 杂志文章

    doi:10.1186/1756-9966-29-40

    authors: Bernardes VF,Gleber-Netto FO,Sousa SF,Silva TA,Aguiar MC

    更新日期:2010-04-29 00:00:00

  • Inhibition of skin carcinogenesis by suppression of NF-κB dependent ITGAV and TIMP-1 expression in IL-32γ overexpressed condition.

    abstract:BACKGROUND:Interleukin-32 (IL-32) has been associated with various diseases. Previous studies have shown that IL-32 inhibited the development of several tumors. However, the role of IL-32γ, an isotype of IL-32, in skin carcinogenesis remains unknown. METHODS:We compared 7,12-Dimethylbenz[a]anthracene/12-O-Tetradecanoy...

    journal_title:Journal of experimental & clinical cancer research : CR

    pub_type: 杂志文章

    doi:10.1186/s13046-018-0943-8

    authors: Lee YS,Lee CH,Bae JT,Nam KT,Moon DB,Hwang OK,Choi JS,Kim TH,Jun HO,Jung YS,Hwang DY,Han SB,Yoon DY,Hong JT

    更新日期:2018-11-28 00:00:00

  • Different p53 genotypes regulating different phosphorylation sites and subcellular location of CDC25C associated with the formation of polyploid giant cancer cells.

    abstract:BACKGROUND:Our previous studies have confirmed that cobalt chloride (CoCl2) can induce the formation of polyploid giant cancer cells (PGCCs), which is the key to the heterogeneity of solid tumors. PGCC formation is closely related to the abnormal expression of cell cycle-related proteins and cell fusion. In this study,...

    journal_title:Journal of experimental & clinical cancer research : CR

    pub_type: 杂志文章

    doi:10.1186/s13046-020-01588-w

    authors: Liu K,Zheng M,Zhao Q,Zhang K,Li Z,Fu F,Zhang H,Du J,Li Y,Zhang S

    更新日期:2020-05-11 00:00:00

  • Nucleolar and spindle associated protein 1 promotes the aggressiveness of astrocytoma by activating the Hedgehog signaling pathway.

    abstract:BACKGROUND:The prognosis of human astrocytoma is poor, and the molecular alterations underlying its pathogenesis still needed to be elucidated. Nucleolar and spindle associated protein 1 (NUSAP1) was observed in several types of cancers, but its role in astrocytoma remained unknown. METHODS:The expression of NUSAP1 in...

    journal_title:Journal of experimental & clinical cancer research : CR

    pub_type: 杂志文章

    doi:10.1186/s13046-017-0597-y

    authors: Wu X,Xu B,Yang C,Wang W,Zhong D,Zhao Z,He L,Hu Y,Jiang L,Li J,Song L,Zhang W

    更新日期:2017-09-12 00:00:00

  • Long non-coding RNA H19 promotes colorectal cancer metastasis via binding to hnRNPA2B1.

    abstract:BACKGROUND:Long non-coding RNA H19 was demonstrated to be significantly correlated with tumor metastasis. However, the specific functions of H19 in colorectal cancer (CRC) metastasis and the underlying mechanism are still largely unclear. METHODS:Use public database to screen the potential lncRNA crucial for metastasi...

    journal_title:Journal of experimental & clinical cancer research : CR

    pub_type: 杂志文章

    doi:10.1186/s13046-020-01619-6

    authors: Zhang Y,Huang W,Yuan Y,Li J,Wu J,Yu J,He Y,Wei Z,Zhang C

    更新日期:2020-07-22 00:00:00

  • SLC29A1 single nucleotide polymorphisms as independent prognostic predictors for survival of patients with acute myeloid leukemia: an in vitro study.

    abstract:BACKGROUND:The mechanism behind poor survival of acute myeloid leukemia (AML) patients with 1-barabinofuranosylcytosine (Ara-C) based treatment remains unclear. This study aimed to assess the pharmacogenomic effects of Ara-C metabolic pathway in patients with AML. METHODS:The genotypes of 19 single nucleotide polymorp...

    journal_title:Journal of experimental & clinical cancer research : CR

    pub_type: 杂志文章,随机对照试验

    doi:10.1186/s13046-014-0090-9

    authors: Wan H,Zhu J,Chen F,Xiao F,Huang H,Han X,Zhong L,Zhong H,Xu L,Ni B,Zhong J

    更新日期:2014-11-15 00:00:00

  • Loss of expression of Kruppel-like factor 6 in primary hepatocellular carcinoma and hepatoma cell lines.

    abstract::KLF6 (Zf9, COPEB), an ubiquitous transcription factor, maps to chromosome 10p. Recently, KLF6 was found to have a more generalized role in tumorigenesis as a candidate tumor suppressor gene for some tumors. However, results from other published studies seem not to be in agreement with data from previous studies. Gene-...

    journal_title:Journal of experimental & clinical cancer research : CR

    pub_type: 杂志文章

    doi:

    authors: Wang SP,Zhou HJ,Chen XP,Ren GY,Ruan XX,Zhang Y,Zhang RL,Chen J

    更新日期:2007-03-01 00:00:00

  • A long-standing cystic lymph-node metastasis from occult thyroid carcinoma.

    abstract::Here we report the case of a patient with a soft tissue mass of the neck. For more than 10 years it was thought to be a branchial cyst and was later diagnosed to be a cystic lymph node metastasis from an occult thyroid carcinoma. ...

    journal_title:Journal of experimental & clinical cancer research : CR

    pub_type: 杂志文章

    doi:

    authors: Appetecchia M,Meçule A,Sciarretta F

    更新日期:2002-03-01 00:00:00

  • A central role for MeCP2 in the epigenetic repression of miR-200c during epithelial-to-mesenchymal transition of glioma.

    abstract:BACKGROUND:The epithelial-to-mesenchymal transition (EMT) has been linked to the regulation of glioma progression. However, the underlying signaling mechanisms that regulate EMT are poorly understood. METHODS:Quantitative real-time PCR (RT-qPCR) and western blot were performed to detect the expression of MeCP2 in glio...

    journal_title:Journal of experimental & clinical cancer research : CR

    pub_type: 杂志文章

    doi:10.1186/s13046-019-1341-6

    authors: Bian E,Chen X,Xu Y,Ji X,Cheng M,Wang H,Fang Z,Zhao B

    更新日期:2019-08-20 00:00:00

  • MiR-302a/b/c/d cooperatively sensitizes breast cancer cells to adriamycin via suppressing P-glycoprotein(P-gp) by targeting MAP/ERK kinase kinase 1 (MEKK1).

    abstract:BACKGROUND:The importance of individual microRNAs (miRNAs) in tumor has been established in different cancers. However, their association with tumor chemoresistance has not been fully understood. Previously, we found two novel MDR-associated microRNAs (miRNAs). In this report, we investigated the combined effects of mi...

    journal_title:Journal of experimental & clinical cancer research : CR

    pub_type: 杂志文章

    doi:10.1186/s13046-016-0300-8

    authors: Zhao L,Wang Y,Jiang L,He M,Bai X,Yu L,Wei M

    更新日期:2016-02-03 00:00:00

  • Mitophagy promotes sorafenib resistance through hypoxia-inducible ATAD3A dependent Axis.

    abstract:BACKGROUND:The identification of novel targets for recovering sorafenib resistance is pivotal for Hepatocellular carcinoma (HCC) patients. Mitophagy is the programmed degradation of mitochondria, and is likely involved in drug resistance of cancer cells. Here, we identified hyperactivated mitophagy is essential for sor...

    journal_title:Journal of experimental & clinical cancer research : CR

    pub_type: 杂志文章

    doi:10.1186/s13046-020-01768-8

    authors: Wu H,Wang T,Liu Y,Li X,Xu S,Wu C,Zou H,Cao M,Jin G,Lang J,Wang B,Liu B,Luo X,Xu C

    更新日期:2020-12-07 00:00:00

  • ERRγ target genes are poor prognostic factors in Tamoxifen-treated breast cancer.

    abstract:BACKGROUND:One-third of estrogen (ER+) and/or progesterone receptor-positive (PGR+) breast tumors treated with Tamoxifen (TAM) do not respond to initial treatment, and the remaining 70% are at risk to relapse in the future. Estrogen-related receptor gamma (ESRRG, ERRγ) is an orphan nuclear receptor with broad, structur...

    journal_title:Journal of experimental & clinical cancer research : CR

    pub_type: 杂志文章

    doi:10.1186/s13046-015-0150-9

    authors: Madhavan S,Gusev Y,Singh S,Riggins RB

    更新日期:2015-05-15 00:00:00

  • Interstitial transfer factor as adjuvant immunotherapy for experimental glioma.

    abstract::Glioblastoma multiform (GBM) is the most common tumour of the central nervous system in humans. Unfortunately its prognosis is poor and because of the lack of efficacious therapies, immunotherapy is a potential treatment. Transfer factors (TF) are low molecular weight dialysable products extracted from immune cells wh...

    journal_title:Journal of experimental & clinical cancer research : CR

    pub_type: 杂志文章

    doi:

    authors: Pineda B,Estrada-Parra S,Pedraza-Medina B,Rodriguez-Ropon A,Pérez R,Arrieta O

    更新日期:2005-12-01 00:00:00

  • Laryngeal endocrinomas (carcinoids and relevant neoplasms): analysis of 278 reported cases.

    abstract::This study was carried out to provide extensive information obtained from statistical analysis of laryngeal endocrinomas for the use of investigators working in this particular research field. A total of 278 patients with both typical and atypical varieties of carcinoids, and with small/oat cell carcinomas (SCC/OCC) e...

    journal_title:Journal of experimental & clinical cancer research : CR

    pub_type: 杂志文章

    doi:

    authors: Soga J,Osaka M,Yakuwa Y

    更新日期:2002-03-01 00:00:00

  • MAZ promotes prostate cancer bone metastasis through transcriptionally activating the KRas-dependent RalGEFs pathway.

    abstract:BACKGROUND:Clinically, prostate cancer (PCa) exhibits a high avidity to metastasize to bone. Myc-associated zinc-finger protein (MAZ) is a well-documented oncogene involved in the progression and metastasis of multiple cancer types, even in PCa. However, the clinical significance and biological roles of MAZ in bone met...

    journal_title:Journal of experimental & clinical cancer research : CR

    pub_type: 杂志文章

    doi:10.1186/s13046-019-1374-x

    authors: Yang Q,Lang C,Wu Z,Dai Y,He S,Guo W,Huang S,Du H,Ren D,Peng X

    更新日期:2019-09-05 00:00:00

  • A dosimetric comparison of different treatment plans of palliative spinal bone irradiation: analysis of dose coverage with respect to ICRU 50 Report.

    abstract:BACKGROUND:This study aimed to analyze three-dimensional (3D) dosimetric data of conventional two-dimensional (2D) palliative spinal bone irradiation using different reference points and treatment plans with respect to the International Commission on Radiation Units and Measurements (ICRU) Report 50. METHODS:Forty-fiv...

    journal_title:Journal of experimental & clinical cancer research : CR

    pub_type: 杂志文章

    doi:10.1186/1756-9966-28-2

    authors: Andic F,Baz Cifci S,Ors Y,Niang U,Dirier A,Adli M

    更新日期:2009-01-07 00:00:00

  • Effects of silencing of mutant p53 gene in human lung adenocarcinoma cell line Anip973.

    abstract::The mutational spectrum of p53 gene and the biological effects of mutant p53 protein vary greatly from one type of tumor to another. To investigate the biological effects of mutant p53 gene in human lung adenocarcinoma, mutant p53 was silenced by RNA interference (RNAi) in cell line Anip973. Then, the effects of mutan...

    journal_title:Journal of experimental & clinical cancer research : CR

    pub_type: 杂志文章

    doi:

    authors: Ma LL,Sun WJ,Wang Zh,Zh GY,Li P,Fu SB

    更新日期:2006-12-01 00:00:00

  • Efficient inhibition of murine breast cancer growth and metastasis by gene transferred mouse survivin Thr34-->Ala mutant.

    abstract:BACKGROUND:Metastasis in breast cancer is a vital concern in treatment because most women with primary breast cancer have micrometastases to distant sites at diagnosis. As a member of the inhibitor of apoptosis protein (IAP) family, survivin has been proposed as an attractive target for new anticancer interventions. In...

    journal_title:Journal of experimental & clinical cancer research : CR

    pub_type: 杂志文章

    doi:10.1186/1756-9966-27-46

    authors: Peng XC,Yang L,Yang LP,Mao YQ,Yang HS,Liu JY,Zhang DM,Chen LJ,Wei YQ

    更新日期:2008-09-25 00:00:00

  • Turcot syndrome: case report and nosological aspects.

    abstract::The Turcot syndrome has been defined as the simultaneous presence of multiple polyposis of the colon and a malignant brain tumor. This association is supposed to be genetically transmitted, even though we still do not exactly know whether this occurs in a dominant or recessive way. The case of a 47-year-old man submit...

    journal_title:Journal of experimental & clinical cancer research : CR

    pub_type: 杂志文章

    doi:

    authors: Fracasso P,Caviglia R,Grassi A,Lapenta R,Stigliano V,Franco D,Casale V

    更新日期:1997-12-01 00:00:00

  • G-quadruplex ligand RHPS4 radiosensitizes glioblastoma xenograft in vivo through a differential targeting of bulky differentiated- and stem-cancer cells.

    abstract:BACKGROUND:Glioblastoma is the most aggressive and most lethal primary brain tumor in the adulthood. Current standard therapies are not curative and novel therapeutic options are urgently required. Present knowledge suggests that the continued glioblastoma growth and recurrence is determined by glioblastoma stem-like c...

    journal_title:Journal of experimental & clinical cancer research : CR

    pub_type: 杂志文章

    doi:10.1186/s13046-019-1293-x

    authors: Berardinelli F,Tanori M,Muoio D,Buccarelli M,di Masi A,Leone S,Ricci-Vitiani L,Pallini R,Mancuso M,Antoccia A

    更新日期:2019-07-16 00:00:00

  • Attenuation of TGFBR2 expression and tumour progression in prostate cancer involve diverse hypoxia-regulated pathways.

    abstract:BACKGROUND:Dysregulation of transforming growth factor β (TGF-β) signaling and hypoxic microenvironment have respectively been reported to be involved in disease progression in malignancies of prostate. Emerging evidence indicates that downregulation of TGFBR2, a pivotal regulator of TGF-β signaling, may contribute to ...

    journal_title:Journal of experimental & clinical cancer research : CR

    pub_type: 杂志文章

    doi:10.1186/s13046-018-0764-9

    authors: Zhou H,Wu G,Ma X,Xiao J,Yu G,Yang C,Xu N,Zhang B,Zhou J,Ye Z,Wang Z

    更新日期:2018-04-27 00:00:00

  • Detection of CD44 variants in fine needle aspiration biopsies of thyroid tumor by RT-PCR.

    abstract::Increased expression of CD44 variants is often observed in differentiated thyroid carcinomas. To establish a method for gene diagnosis of thyroid without any additional invasions to the patients, RNA in leftover cells inside the needle used for fine needle aspiration biopsies (FNABs) was extracted to detect the expres...

    journal_title:Journal of experimental & clinical cancer research : CR

    pub_type: 杂志文章

    doi:

    authors: Takano T,Sumizaki H,Amino N

    更新日期:1997-09-01 00:00:00

  • m6A modification in RNA: biogenesis, functions and roles in gliomas.

    abstract::The chemical modification of RNA is a newly discovered epigenetic regulation mechanism in cells and plays a crucial role in a variety of biological processes. N6-methyladenine (m6A) mRNA modification is the most abundant form of posttranscriptional RNA modification in eukaryotes. Through the development of m6A RNA seq...

    journal_title:Journal of experimental & clinical cancer research : CR

    pub_type: 杂志文章,评审

    doi:10.1186/s13046-020-01706-8

    authors: Zhang Y,Geng X,Li Q,Xu J,Tan Y,Xiao M,Song J,Liu F,Fang C,Wang H

    更新日期:2020-09-17 00:00:00

  • Flow cytometric analysis of CK19 expression in the peripheral blood of breast carcinoma patients: relevance for circulating tumor cell detection.

    abstract:BACKGROUND:Immunocytochemistry and RT-PCR have been widely used for the detection of circulating tumor cells in patients with breast cancer but their specificity is limited. Our purpose is to utilize a convenient and specific technology to detect circulating tumor cells in breast cancer patients. METHODS:To determine ...

    journal_title:Journal of experimental & clinical cancer research : CR

    pub_type: 杂志文章

    doi:10.1186/1756-9966-28-57

    authors: Wang L,Wang Y,Liu Y,Cheng M,Wu X,Wei H

    更新日期:2009-04-28 00:00:00

  • PCBP1 depletion promotes tumorigenesis through attenuation of p27Kip1 mRNA stability and translation.

    abstract:BACKGROUND:Poly C Binding Protein 1 (PCBP1) is an RNA-binding protein that binds and regulates translational activity of subsets of cellular mRNAs. Depletion of PCBP1 is implicated in various carcinomas, but the underlying mechanism in tumorigenesis remains elusive. METHODS:We performed a transcriptome-wide screen to ...

    journal_title:Journal of experimental & clinical cancer research : CR

    pub_type: 杂志文章

    doi:10.1186/s13046-018-0840-1

    authors: Shi H,Li H,Yuan R,Guan W,Zhang X,Zhang S,Zhang W,Tong F,Li L,Song Z,Wang C,Yang S,Wang H

    更新日期:2018-08-07 00:00:00

  • Intrinsic fluorescence of the clinically approved multikinase inhibitor nintedanib reveals lysosomal sequestration as resistance mechanism in FGFR-driven lung cancer.

    abstract:BACKGROUND:Studying the intracellular distribution of pharmacological agents, including anticancer compounds, is of central importance in biomedical research. It constitutes a prerequisite for a better understanding of the molecular mechanisms underlying drug action and resistance development. Hyperactivated fibroblast...

    journal_title:Journal of experimental & clinical cancer research : CR

    pub_type: 杂志文章

    doi:10.1186/s13046-017-0592-3

    authors: Englinger B,Kallus S,Senkiv J,Heilos D,Gabler L,van Schoonhoven S,Terenzi A,Moser P,Pirker C,Timelthaler G,Jäger W,Kowol CR,Heffeter P,Grusch M,Berger W

    更新日期:2017-09-07 00:00:00