Article

Circulating microRNA Profiling Identifies a Subset of Metastatic Prostate Cancer Patients with Evidence of Cancer-Associated Hypoxia

Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America
PLoS ONE (Impact Factor: 3.23). 07/2013; 8(7):e69239. DOI: 10.1371/journal.pone.0069239
Source: PubMed

ABSTRACT

MicroRNAs (miRNAs) are small (∼22 nucleotide) non-coding RNAs that regulate a myriad of biological processes and are frequently dysregulated in cancer. Cancer-associated microRNAs have been detected in serum and plasma and hold promise as minimally invasive cancer biomarkers, potentially for assessing disease characteristics in patients with metastatic disease that is difficult to biopsy. Here we used miRNA profiling to identify cancer-associated miRNAs that are differentially expressed in sera from patients with metastatic castration resistant prostate cancer (mCRPC) as compared to healthy controls. Of 365 miRNAs profiled, we identified five serum miRNAs (miR-141, miR-200a, miR-200c, miR-210 and miR-375) that were elevated in cases compared to controls across two independent cohorts. One of these, miR-210, is a known transcriptional target of the hypoxia-responsive HIF-1α signaling pathway. Exposure of cultured prostate cancer cells to hypoxia led to induction of miR-210 and its release into the extracellular environment. Moreover, we found that serum miR-210 levels varied widely amongst mCRPC patients undergoing therapy, and correlated with treatment response as assessed by change in PSA. Our results suggest that (i) cancer-associated hypoxia is a frequent, previously under-appreciated characteristic of mCRPC, and (ii) serum miR-210 may be further developed as a predictive biomarker in patients with this distinct disease biology.

Download full-text

Full-text

Available from: Arul M Chinnaiyan, Feb 19, 2014
  • Source
    • "Similar to miR-141, circulating miR-375 levels have been correlated to the Gleason score, lymph node status, and distant metastasis (Brase et al., 2011). The amount of miR- 375 increases from low-risk through high-risk localized disease toward metastatic cancer (Bryant et al., 2012; Selth et al., 2012; Cheng et al., 2013; Nguyen et al., 2013). Porkka et al. (2007) have shown that let-7c and miR-30c are with decreased expression in tissues of PC patients compared to tissues from BPH patients. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The traditional Chinese medicinal formula BDL301 has been used to inhibit inflammation for hundreds of years. The development of colorectal cancer and chronic inflammation are closely related. In this study, we investigated whether BDL301 could inhibit tumor growth. We found that angiogenesis and tumor growth were both inhibited in vivo. In addition, apoptosis was induced and the signal transducer and activator of transcription-3 (STAT3) pathway were suppressed in the colorectal cancer cells in vitro and in vivo by BDL301. This study demonstrates that BDL301 exerted significant anticancer activity by inhibiting the STAT3 pathways and inducing apoptosis in colorectal cancer cells.
    Preview · Article · Jan 2015 · DNA and Cell Biology
  • Source
    • "Similar to miR-141, circulating miR-375 levels have been correlated to the Gleason score, lymph node status, and distant metastasis (Brase et al., 2011). The amount of miR- 375 increases from low-risk through high-risk localized disease toward metastatic cancer (Bryant et al., 2012; Selth et al., 2012; Cheng et al., 2013; Nguyen et al., 2013). Porkka et al. (2007) have shown that let-7c and miR-30c are with decreased expression in tissues of PC patients compared to tissues from BPH patients. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The endomembrane system plays an important role during cellular adaptation of the plants with the extracellular environment. The small GTP-binding protein Rab7 located at the vacuolar membrane regulates the vesicle fusion with the vacuole and thereby helps in recycling of the molecules. This is the first report on isolation and characterization of AlRab7 gene from the halophyte plant, Aeluropus that extrudes NaCl through salt glands and grows luxuriantly throughout the year at the Gujarat coast, India. The AlRab7 encodes a protein with 206 amino acids, and a highly conserved effector-binding domain and four nucleotide-binding domains. The in silico analysis predicts the presence of the prenylation site for Rab geranylgeranyltransferase 2 and the Rab escort protein site. The C-terminal two cysteine residues in -XCC sequence are present for membrane attachment. Transcript expression of the AlRab7 gene was differentially regulated by different environmental stimuli such as dehydration, salinity, and hormone abscisic acid (ABA). The recombinant Escherichia coli cells showed improved growth in Luria Bertani medium supplemented with NaCl, KCl, mannitol, ABA, and indole-3-acetic acid. A novel Rab7 interacting partner AlRabring7 was identified by yeast two-hybrid screening.
    Full-text · Article · Nov 2014 · DNA and Cell Biology
  • Source
    • "Only a few studies have investigated the levels of (circulating) miRNAs as therapeutic markers. The investigations that evaluated potential biomarkers in metastatic PCa and/or CRPC are limited by the number of patients and tested miRNAs [9, 109–111, 118]. In these studies, the researcher investigated upregulated circulating miRNAs in serum of CRPC patients that are applicable candidates as markers for therapeutic response. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Prostate cancer (PCa) is the second most common diagnosed malignant disease in men worldwide. Although serum PSA test dramatically improved the early diagnosis of PCa, it also led to an overdiagnosis and as a consequence to an overtreatment of patients with an indolent disease. New biomarkers for diagnosis, prediction, and monitoring of the disease are needed. These biomarkers would enable the selection of patients with aggressive or progressive disease and, hence, would contribute to the implementation of individualized therapy of the cancer patient. Since the FDA approval of the long noncoding PCA3 RNA-based urine test for the diagnosis of PCa patients, many new noncoding RNAs (ncRNAs) associated with PCa have been discovered. According to their size and function, ncRNAs can be divided into small and long ncRNAs. NcRNAs are expressed in (tumor) tissue, but many are also found in circulating tumor cells and in all body fluids as protein-bound or incorporated in extracellular vesicles. In these protected forms they are stable and so they can be easily analyzed, even in archival specimens. In this review, the authors will focus on ncRNAs as novel biomarker candidates for PCa diagnosis, prediction, prognosis, and monitoring of therapeutic response and discuss their potential for an implementation into clinical practice.
    Full-text · Article · Aug 2014 · BioMed Research International
Show more