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
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microRNA-133b downregulation and inhibition of cell proliferation, migration and invasion by targeting matrix metallopeptidase‑9 in renal cell carcinoma
TL;DR: Evidence that miRNA-133b suppresses cell proliferation, migration and invasion by targeting MMP-9 in RCC cell lines is provided and it is suggested that mi RNA-133B may be used for the development of novel molecular markers and therapeutic approaches to inhibit the metastasis of RCC.
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Differential expression of miR-195 in esophageal squamous cell carcinoma and miR-195 expression inhibits tumor cell proliferation and invasion by targeting of Cdc42
Mingen Fu,Shuo Li,Tingting Yu,Li-juan Qian,Risheng Cao,Hong Zhu,Bin Xiao,Chunhua Jiao,Na-na Tang,Jingjing Ma,Jie Hua,Weifeng Zhang,Hongjie Zhang,Ruihua Shi +13 more
TL;DR: It is demonstrated that miR‐195 may act as a tumor suppressor in ESCC by targeting Cdc42.
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miR-133a inhibits cervical cancer growth by targeting EGFR
TL;DR: Results showed that miR-133a suppresses cervical cancer growth in vitro and in–vivo through targeting EGFR, suggesting that miD-133A can be a potential target for the treatment of cervical cancer.
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The p53/microRNA connection in gastrointestinal cancer
TL;DR: The state-of-the-art on the role of the p53-miRNA connection in gastrointestinal cancer is summarized and miRNA-based therapeutics may represent a feasible strategy for future cancer treatment.
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MicroRNAs in esophageal cancer (review).
TL;DR: Accumulating evidence suggests that the deregulation of miRNAs not only results in cancer progression, but also directly promotes tumor initiation, indicating that miRNA expression is important in tumorigenesis.
References
More filters
Journal ArticleDOI
MicroRNAs: Genomics, Biogenesis, Mechanism, and Function
TL;DR: Although they escaped notice until relatively recently, miRNAs comprise one of the more abundant classes of gene regulatory molecules in multicellular organisms and likely influence the output of many protein-coding genes.
Journal ArticleDOI
The functions of animal microRNAs
TL;DR: Evidence is mounting that animal miRNAs are more numerous, and their regulatory impact more pervasive, than was previously suspected.
Journal Article
MicroRNA signatures in human cancers
George A. Calin,Carlo M. Croce +1 more
TL;DR: The causes of the widespread differential expression of miRNA genes in malignant compared with normal cells can be explained by the location of these genes in cancer-associated genomic regions, by epigenetic mechanisms and by alterations in the miRNA processing machinery as discussed by the authors.
Journal ArticleDOI
MicroRNAs: small RNAs with a big role in gene regulation
Lin He,Gregory J. Hannon +1 more
TL;DR: Two founding members of the microRNA family were originally identified in Caenorhabditis elegans as genes that were required for the timed regulation of developmental events and indicate the existence of multiple RISCs that carry out related but specific biological functions.
Journal Article
Oncomirs : microRNAs with a role in cancer
TL;DR: I MicroRNAs (miRNAs) are an abundant class of small non-protein-coding RNAs that function as negative gene regulators as discussed by the authors, and have been shown to repress the expression of important cancer-related genes and might prove useful in the diagnosis and treatment of cancer.