Abstract
Cancer progression depends on tumor growth and metastasis, which are activated or suppressed by multiple genes. An individual microRNA may target multiple genes, suggesting that a miRNA may suppress tumor growth and metastasis via simultaneously targeting different genes. However, thus far, this issue has not been explored. In the present study, the findings showed that miR-1 could simultaneously inhibit tumor growth and metastasis of gastric and breast cancers by targeting multiple genes. The results indicated that miR-1 was significantly downregulated in cancer tissues compared with normal tissues. The miR-1 overexpression led to cell cycle arrest in the G1 phase in gastric and breast cancer cells but not in normal cells. Furthermore, the miR-1 overexpression significantly inhibited the metastasis of gastric and breast cancer cells. An analysis of the underlying mechanism revealed that the simultaneous inhibition of tumor growth and metastasis mediated by miR-1 was due to the synchronous targeting of 6 miR-1 target genes encoding cyclin dependent kinase 4, twinfilin actin binding protein 1, calponin 3, coronin 1C, WAS protein family member 2 and thymosin beta 4, X-linked. In vivo assays demonstrated that miR-1 efficiently inhibited tumor growth and metastasis of gastric and breast cancers in nude mice. Therefore, our study contributed novel insights into the miR-1′s roles in tumorigenesis of gastric and breast cancers.
Highlights
Cancer is the most common cause of disease-related death in humans worldwide, with more than 10 million new cases every year [1]
An analysis of the underlying mechanism revealed that the simultaneous inhibition of tumor growth and metastasis mediated by miR-1 was due to the synchronous targeting of 6 miR-1 target genes encoding cyclin dependent kinase 4, twinfilin actin binding protein 1, calponin 3, coronin 1C, WAS protein family member 2 and thymosin beta 4, X-linked
The results indicated that there was a significant correlation between miR-1 expression level and tumorigenesis (Figure 1D)
Summary
Cancer is the most common cause of disease-related death in humans worldwide, with more than 10 million new cases every year [1]. The inhibition of tumor growth and metastatic dissemination is the primary challenge of cancer therapy. Standard cancer treatments currently include surgical intervention, radiation and chemotherapeutic drugs. Radiation and chemotherapeutic drugs can kill normal cells and cause toxicity in patients. Many chemotherapeutic drugs targeting cancer-related molecules have been discovered and tested in clinical trials due to an improved understanding of tumor biology. ZSKT474, a PI3K inhibitor, suppresses tumor growth by inducing G0/G1 arrest and is in a phase I clinical trial for the treatment of solid tumors [3]. The RAS proteins, key regulators of malignant transformation, are aberrantly expressed in most human tumors. Rational www.impactjournals.com/oncotarget therapies that target the RAS pathways may inhibit tumor growth, survival and metastasis [5, 6]. Tumor development and metastasis depend on the regulation of gene expression. As novel cancer therapeutic agents, microRNAs (miRNAs) have attracted an increasing amount of attention for their capacity to activate or suppress tumor-associated gene expression
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