miR-145, miR-133a and miR-133b: Tumor-suppressive miRNAs target FSCN1 in esophageal squamous cell carcinoma
Masayuki Kano,Naohiko Seki,Naoko Kikkawa,Lisa Fujimura,Isamu Hoshino,Yasunori Akutsu,Takeshi Chiyomaru,Hideki Enokida,Masayuki Nakagawa,Hisahiro Matsubara +9 more
TLDR
The identification of tumor‐suppressive miRNAs,miR‐145, miR‐133a and miR-133b, directly control oncogenic FSCN1 gene, and could provide new insights into potential mechanisms of ESCC carcinogenesis.Abstract:
MicroRNAs (miRNAs), noncoding RNAs 21–25 nucleotides in length, regulate gene expression primarily at the posttranscriptional level. Growing evidence suggests that miRNAs are aberrantly expressed in many human cancers, and that they play significant roles in carcinogenesis and cancer progression. A search for miRNAs with a tumor-suppressive function in esophageal squamous cell carcinoma (ESCC) was performed using the miRNA expression signatures obtained from ESCC clinical specimens. A subset of 15 miRNAs was significantly downregulated in ESCC. A comparison of miRNA signatures from ESCC and our previous report identified 4 miRNAs that are downregulated in common (miR-145, miR-30a-3p, miR-133a and miR-133b), suggesting that these miRNAs are candidate tumor suppressors. Gain-of-function analysis revealed that 3 transfectants (miR-145, miR-133a and miR-133b) inhibit cell proliferation and cell invasion in ESCC cells. These miRNAs (miR-145, miR-133a and miR-133b), which have conserved sequences in the 3′UTR of FSCN1 (actin-binding protein, Fascin homolog 1), inhibited FSCN1 expression. The signal from a luciferase reporter assay was significantly decreased at 2 miR-145 target sites and 1 miR-133a/b site, suggesting both miRNAs directly regulate FSCN1. An FSCN1 loss-of-function assay found significant cell growth and invasion inhibition, implying an FSCN1 is associated with ESCC carcinogenesis. The identification of tumor-suppressive miRNAs, miR-145, miR-133a and miR-133b, directly control oncogenic FSCN1 gene. These signal pathways of ESCC could provide new insights into potential mechanisms of ESCC carcinogenesis.read more
Citations
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MiR-133b targets antiapoptotic genes and enhances death receptor-induced apoptosis.
Juan Pablo Patron,Annika Fendler,Annika Fendler,Matthias Bild,Ulrike Jung,Henrik Müller,Magnus Ø. Arntzen,Magnus Ø. Arntzen,Magnus Ø. Arntzen,Chloe Piso,Carsten Stephan,Bernd Thiede,Hans-Joachim Mollenkopf,Klaus Jung,Stefan H. E. Kaufmann,Joerg Schreiber +15 more
TL;DR: The ability of a single miR to influence major apoptosis pathways is revealed, suggesting an essential role for this molecule during cellular transformation, tumorigenesis and tissue homeostasis.
Journal ArticleDOI
The role of microRNAs in cancers of the upper gastrointestinal tract
Shumei Song,Jaffer A. Ajani +1 more
TL;DR: The growing body of evidence regarding the alterations of miRNAs in UGICs is reviewed, finding that suppressing translation and/or promoting degradation of mRNAs can contribute to carcinogenesis and progression of UG ICs.
Journal ArticleDOI
MiR-133a induces apoptosis through direct regulation of GSTP1 in bladder cancer cell lines
Yousuke Uchida,Takeshi Chiyomaru,Hideki Enokida,Kazumori Kawakami,Shuichi Tatarano,Kazuya Kawahara,Kenryu Nishiyama,Naohiko Seki,Masayuki Nakagawa +8 more
TL;DR: The data suggest that tumor suppressive miR-133a directly regulated oncogenic GSTP 1 gene in BC, and that an anti-apoptotic effect mediated by GSTP1 is maintained by miR -133a down-regulation in human BC.
Journal ArticleDOI
Mir-148a improves response to chemotherapy in sensitive and resistant oesophageal adenocarcinoma and squamous cell carcinoma cells.
Richard Hummel,Richard Hummel,David I. Watson,Cameron M Smith,Jakob W. Kist,Michael Michael,Joerg Haier,Damian J. Hussey +7 more
TL;DR: MiR-148a sensitized chemotherapy-sensitive oesophageal cancer cell lines to cisplatin and, to a lesser extent, to 5-flurouracil and attenuated resistance in chemotherapy-resistant variants.
Journal ArticleDOI
MicroRNA expression signatures during malignant progression from Barrett's esophagus to esophageal adenocarcinoma.
Xifeng Wu,Jaffer A. Ajani,Jian Gu,David W. Chang,Weiqi Tan,Michelle A.T. Hildebrandt,Maosheng Huang,Kenneth K. Wang,Ernest T. Hawk +8 more
TL;DR: A genome-wide profiling of 754 human microRNAs (miRNAs) in 35 normal epithelium, 34 Barrett's esophagus, and 36 esophageal adenocarcinoma tissues using TaqMan real-time PCR-based profiling identified a number of novel miRNAs that showed progressively altered expression, including miR-301b, mi-618, and mi-23b.
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