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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MiR-133b is frequently decreased in gastric cancer and its overexpression reduces the metastatic potential of gastric cancer cells
Yu Zhao,Jie Huang,Li Zhang,Ying Qu,Jianfang Li,Beiqin Yu,Min Yan,Yingyan Yu,Bingya Liu,Zhenggang Zhu +9 more
TL;DR: Overexpression of miR-133b inhibits cell metastasis in vitro and in vivo partly by directly suppressing expression of Gli1 protein.
Journal ArticleDOI
Alteration of serum miR-206 and miR-133b is associated with lung carcinogenesis induced by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone
Jianjun Wu,Ti Yang,Xun Li,Qiaoyuan Yang,Rong Liu,Jinkun Huang,Yuanqi Li,Chengfeng Yang,Yiguo Jiang +8 more
TL;DR: It is demonstrated that lung carcinogen NNK exposure changes the expression of serum miRNAs, which could be associated with lung carcinogenesis induced by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK).
Journal ArticleDOI
The role of microRNA-133b and its target gene FSCN1 in gastric cancer.
Lihua Guo,Lihua Guo,Hua Bai,Dongling Zou,Tao Hong,Jie Liu,Jiaqiang Huang,Pengfei He,Qi Zhou,Jinsheng He +9 more
TL;DR: Investigation of the detailed mechanism showed that miR-133b directly targeted FSCN1 which functioned as an oncogenic gene in GC cells and exerted its tumor suppressor role inGC cells.
Journal ArticleDOI
microRNA-504 inhibits cancer cell proliferation via targeting CDK6 in hypopharyngeal squamous cell carcinoma.
Naoko Kikkawa,Takashi Kinoshita,Nijiro Nohata,Toyoyuki Hanazawa,Noriko Yamamoto,Ichiro Fukumoto,Takeshi Chiyomaru,Hideki Enokida,Masayuki Nakagawa,Yoshitaka Okamoto,Naohiko Seki +10 more
TL;DR: This study confirmed the downregulation of miR-504 in HSCC clinical specimens and identified novel targets regulated by this miRNA in HS CC cells, which provided new insights into HSCC oncogenesis.
Journal ArticleDOI
Downregulation of miR-145 contributes to lung adenocarcinoma cell growth to form brain metastases
Chunyang Zhao,Yan Xu,Yong-Qiang Zhang,Wei-Wei Tan,Jianxin Xue,Zong-Ze Yang,You Zhang,You Lu,Xun Hu +8 more
TL;DR: It is found that the expression of miR-145 can regulate the ability of proliferation of A549 and SPC-A1 cells in vitro, but is not related to lymph node metastasis, migration and invasion.
References
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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.