Downregulation of Sec23A protein by miRNA-375 in prostate carcinoma.
نویسندگان
چکیده
Prostate carcinoma (CaP) is a leading cause of cancer-related death in men. We have previously determined the microRNA (miRNA) profile of primary CaP in comparison with nontumor prostate tissue. miRNAs are small, noncoding RNAs that inhibit protein synthesis on a posttranscriptional level by binding to the 3'-untranslated region (3'-UTR) of their target genes. In primary CaP tissue, we have previously found by miRNA sequencing that miR-375 and miR-200c were upregulated 9.1- and 4.5-fold, respectively. A computational analysis predicted the 3'-UTR of the SEC23A gene as a potential target for both miR-375 and miR-200c. Here, we show that the 3'-UTR of SEC23A mRNA is indeed a target for miR-375 and miR-200c and that both miRNAs downregulate Sec23A protein expression when ectopically expressed in human 293T cells. In primary samples of CaP, we found a direct correlation between reduction of SEC23A mRNA and overexpression of miR-375 but not of miR-200c. The reduced levels of Sec23A protein were inversely correlated to the increased amount of miR-375 in the LNCaP and DU145 CaP cell lines when compared with normal prostate fibroblasts. In primary CaP, we also detected decreased amounts of Sec23A protein when compared with corresponding normal prostate tissue. Ectopically overexpressed Sec23A in LNCaP and DU145 CaP cells significantly reduced the growth properties, indicating that Sec23A might play a role in the induction or growth of prostate carcinoma. Sec23A overexpression reduced cell growth but did not induce apoptosis, whereas inhibition of Sec23A stimulated cell proliferation.
منابع مشابه
Signaling and Regulation Downregulation of Sec23A Protein by miRNA-375 in Prostate Carcinoma
Prostate carcinoma (CaP) is a leading cause of cancer-related death in men. We have previously determined the microRNA (miRNA) profile of primary CaP in comparison with nontumor prostate tissue. miRNAs are small, noncoding RNAs that inhibit protein synthesis on a posttranscriptional level by binding to the 30-untranslated region (30-UTR) of their target genes. In primary CaP tissue, we have pre...
متن کاملComparative microRNA profiling of prostate carcinomas with increasing tumor stage by deep sequencing.
UNLABELLED MicroRNAs (miRNA) posttranscriptionally regulate gene expression and are important in tumorigenesis. Previous deep sequencing identified the miRNA profile of prostate carcinoma versus nonmalignant prostate tissue. Here, we generated miRNA expression profiles of prostate carcinoma by deep sequencing, with increasing tumor stage relative to corresponding nonmalignant and healthy prosta...
متن کاملMicroRNA-375/SEC23A as biomarkers of the in vitro efficacy of vandetanib
In this study, we performed microRNA (miRNA) expression profiling on a large series of sporadic and hereditary forms of medullary thyroid carcinomas (MTC). More than 60 miRNAs were significantly deregulated in tumor vs adjacent non-tumor tissues, partially overlapping with results of previous studies. We focused our attention on the strongest up-regulated miRNA in MTC samples, miR-375, the dere...
متن کاملAnalyzing the Expression Level and Associated Clinical Characteristics of miRNA-138 in Esophageal Squamous Cell Carcinoma in Iranian Patients
Background: Esophageal Squamous Cell Carcinoma (ESCC) is the seventh most common and lethal malignancy worldwide with a high incidence in Iran. Esophageal cancer has a poor prognosis and low 5-years survival rate. Despite several studies on esophageal cancer, its underlying mechanism remains unclear. Therefore, it is significant to analyze the molecular factors involved in disease for introduci...
متن کاملDownregulation of Kinesin Spindle Protein Inhibits Proliferation, Induces Apoptosis and Increases Chemosensitivity in Hepatocellular Carcinoma Cells
Background: Kinesin spindle protein (KSP) plays a critical role in mitosis. Inhibition of KSP function leads to cell cycle arrest at mitosis and ultimately to cell death. The aim of this study was to suppress KSP expression by specific small-interfering RNA (siRNA) in Hep3B cells and evaluate its anti-tumor activity. Methods: Three siRNA targeting KSP (KSP-siRNA #1-3) and one mismatched-siRNA (...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Molecular cancer research : MCR
دوره 9 6 شماره
صفحات -
تاریخ انتشار 2011