Carboplatin-docetaxel-induced activity against ovarian cancer is dependent on up-regulated lncRNA PVT1.

Ovarian cancer is the fourth most ordinary cause of cancer-related deaths in women. In recent, combination chemotherapy with carboplatin and docetaxel was developed as first-line drug to treat ovarian carcinoma. However, the detailed molecular mechanism, which accounts for the cells to apoptosis induced by administration of carboplatin and docetaxel, was unrecognized. In present study, we provide the mechanistic link between mixture of carboplatin plus docetaxel and its anticancer activity. Primarily, a majority of 30 cancer-related long non-coding RNA (lncRNA) showed differential alteration in carboplatin-docetaxel-treated 3AO cells. Among six up-regulating lncRNAs, we screened out carboplatin-docetaxel-induced lncRNA PVT1 which may be a central downstream target of carboplatin plus docetaxel because expression of PVT1 positively correlates with anticancer action of carboplatin plus docetaxel. Besides, p53 and tissue inhibitor of matrix metalloproteinases-1 (TIMP1) were mediated by lncRNA PVT1, which may explain partially the anticancer activity of lncRNA PVT1. Collectively, we have identified a potential mechanism by which PVT1 regulated by carboplatin plus docetaxel contributes to the carboplatin-docetaxel-induced anticancer action in ovarian cancer. These discoveries also give proof of the potential of PVT1 as significant downstream targets for therapeutic intervention in ovarian cancer.

[1]  M V Chernov,et al.  A chemical inhibitor of p53 that protects mice from the side effects of cancer therapy. , 1999, Science.

[2]  Robert L Moritz,et al.  Identification of DIABLO, a Mammalian Protein that Promotes Apoptosis by Binding to and Antagonizing IAP Proteins , 2000, Cell.

[3]  R. Alvarez,et al.  Phase I trial of a formulated IL-12 plasmid in combination with carboplatin and docetaxel chemotherapy in the treatment of platinum-sensitive recurrent ovarian cancer. , 2013, Gynecologic oncology.

[4]  A. Ramani,et al.  SYNDROME OF INAPPROPRIATE ANTIDIURETIC HORMONE SECRETION , 1987, The Journal of the Association of Physicians of India.

[5]  Howard Y. Chang,et al.  The NeST Long ncRNA Controls Microbial Susceptibility and Epigenetic Activation of the Interferon-γ Locus , 2013, Cell.

[6]  K. Zatloukal,et al.  Characterization of HULC, a novel gene with striking up-regulation in hepatocellular carcinoma, as noncoding RNA. , 2007, Gastroenterology.

[7]  Michael F. Lin,et al.  Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals , 2009, Nature.

[8]  R. Agarwal,et al.  Ovarian cancer: strategies for overcoming resistance to chemotherapy , 2003, Nature Reviews Cancer.

[9]  Howard Y. Chang,et al.  Long noncoding RNAs and human disease. , 2011, Trends in cell biology.

[10]  S. Hanash,et al.  Proteomic Analysis of Ovarian Cancer Cells Reveals Dynamic Processes of Protein Secretion and Shedding of Extra-Cellular Domains , 2008, PloS one.

[11]  R. Khokha,et al.  Transgenic TIMP-1 inhibits simian virus 40 T antigen-induced hepatocarcinogenesis by impairment of hepatocellular proliferation and tumor angiogenesis. , 1999, Laboratory investigation; a journal of technical methods and pathology.

[12]  Howard Y. Chang,et al.  Long noncoding RNA HOTAIR reprograms chromatin state to promote cancer metastasis , 2010, Nature.

[13]  K. Darcy,et al.  Current Approaches and Challenges in Managing and Monitoring Treatment Response in Ovarian Cancer , 2014, Journal of Cancer.

[14]  Cole Trapnell,et al.  Integrative annotation of human large intergenic noncoding RNAs reveals global properties and specific subclasses. , 2011, Genes & development.

[15]  David I. Smith,et al.  LSINCT5 is over expressed in breast and ovarian cancer and affects cellular proliferation , 2011, RNA biology.

[16]  N. Turner,et al.  Syndrome of inappropriate anti‐diuretic hormone secretion secondary to carboplatin after docetaxel‐carboplatin‐trastuzumab combination for early stage HER‐2 positive breast cancer , 2012, Asia-Pacific journal of clinical oncology.

[17]  J. Lee,et al.  Forty years of decoding the silence in X-chromosome inactivation. , 2001, Human molecular genetics.

[18]  J. Trent,et al.  WAF1, a potential mediator of p53 tumor suppression , 1993, Cell.

[19]  C. Croce,et al.  microRNA-29 can regulate expression of the long non-coding RNA gene MEG3 in hepatocellular cancer , 2011, Oncogene.

[20]  Yuri Lazebnik,et al.  Identification of Omi/HtrA2 as a Mitochondrial Apoptotic Serine Protease That Disrupts Inhibitor of Apoptosis Protein-Caspase Interaction* , 2002, The Journal of Biological Chemistry.

[21]  H. Yoshiji,et al.  Tissue inhibitor of metalloproteinases‐1 (TIMP‐1) inhibits tumor growth and angiogenesis in the TIMP‐1 transgenic mouse model , 2003, International journal of cancer.

[22]  M. Jordan,et al.  Antiproliferative Mechanism of Action of the Novel Taxane Cabazitaxel as Compared with the Parent Compound Docetaxel in MCF7 Breast Cancer Cells , 2014, Molecular Cancer Therapeutics.

[23]  Howard Y. Chang,et al.  Extensive and coordinated transcription of noncoding RNAs within cell cycle promoters , 2011, Nature Genetics.

[24]  J. Thigpen,et al.  A Phase 3 Trial of Bevacizumab in Ovarian Cancer , 2012 .

[25]  Fangting Wu,et al.  LncRNA loc285194 is a p53-regulated tumor suppressor , 2013, Nucleic acids research.

[26]  J. Rinn,et al.  Large non-coding RNAs: missing links in cancer? , 2010, Human molecular genetics.

[27]  J. Fata,et al.  Host TIMP-1 overexpression confers resistance to experimental brain metastasis of a fibrosarcoma cell line , 1998, Oncogene.

[28]  Yimin Zhu,et al.  Lentiviral vector-mediated upregulation of let-7a inhibits gastric carcinoma cell growth in vitro and in vivo , 2011, Scandinavian journal of gastroenterology.

[29]  L. Kèlland,et al.  The resurgence of platinum-based cancer chemotherapy , 2007, Nature Reviews Cancer.

[30]  John Calvin Reed,et al.  Tumor suppressor p53 is a direct transcriptional activator of the human bax gene , 1995, Cell.

[31]  J. Thigpen Phase III Randomized Trial of Docetaxel-Carboplatin Versus Paclitaxel-Carboplatin as First-Line Chemotherapy for Ovarian Carcinoma , 2006 .

[32]  D. S. Gross,et al.  Chromatin , 2020, Definitions.