MicroRNA-103 suppresses tumor cell proliferation by targeting PDCD10 in prostate cancer.
TL;DR: It is found that miR‐103 is down‐regulated in prostate cancer and closely associated with tumor proliferation and migration.
Abstract: BACKGROUND
It is known that microRNAs (miRNAs) are a class of small, non-coding RNAs that act as key regulators in various physiological and pathological processes. However, the regulatory mechanisms involving miRNAs in prostate cancer remain largely unknown. Here, we found that miR-103 is down-regulated in prostate cancer and closely associated with tumor proliferation and migration. Our objective was to explore the role of the miR-103 in prostate cancer.
METHODS
In this study, we measured miR-103 level using real-time polymerase chain reaction in the human prostate cancer cell lines, including PC-3, LNCap, 22Rv1, DU145, and the normal prostate epithelium cell line RWPE-1, a total of 25 pairs of primary prostate cancer tissues and adjacent non-cancerous tissues (NCTs) were measured also. In addition, over-expression of miR-103 in prostate cancer cell lines to determine the role of miR-103 in prostate cancer.
RESULTS
We found that miR-103 is down-regulated in prostate cancer and closely associated with tumor proliferation and migration. In addition, over-expression of miR-103 apparently inhibits prostate cancer cell proliferation and migration in vitro. Gain-of-function in vitro experiments further show that miR-103 mimics significantly inhibited prostate cancer cell proliferation, invasion and increase the cell cycle in G1 phase, while promoted cell apoptosis. Subsequent dual-luciferase reporter assay identified one of the proto-oncogene PDCD10 as direct target of miR-103.
CONCLUSIONS
Therefore, our data collectively demonstrate that miR-103 is a proto-oncogene miRNA that can suppress prostate cancer proliferation and migration by down-regulating the oncogene PDCD10, indicating that miR-103 may represent a new potential diagnostic and therapeutic target for prostate cancer treatment. Prostate © 2016 Wiley Periodicals, Inc.
Citations
More filters
01 Jan 2009
TL;DR: In this article, a review outlines the current understanding of miRNA target recognition in animals and discusses the widespread impact of miRNAs on both the expression and evolution of protein-coding genes.
Abstract: MicroRNAs (miRNAs) are endogenous ∼23 nt RNAs that play important gene-regulatory roles in animals and plants by pairing to the mRNAs of protein-coding genes to direct their posttranscriptional repression. This review outlines the current understanding of miRNA target recognition in animals and discusses the widespread impact of miRNAs on both the expression and evolution of protein-coding genes.
646 citations
TL;DR: Hepatoma cell‐secreted exosomal miR‐103 increases vascular permeability and promotes tumor metastasis by targeting multiple endothelial junction proteins, which highlights secreted miR•103 as a potential therapeutic target and a predictive marker for HCC metastasis.
231 citations
TL;DR: Results suggested that miR-103 overexpression could contribute to tumor progression by suppressing KLF4, and it might serve as a promising candidate for the prognosis of GC patients.
Abstract: MicroRNAs (miRNAs) play important roles in the cancer development and progression; overexpression of miR-103 has been identified in various tumors. However, its biological function and regulatory mechanism involved in modulation of human gastric cancer (GC) remain largely unknown. This study aimed to confirm clinical significance of miR-103 and investigate its biological role and underlying mechanism in GC. Real-time quantitative PCR (qRT-PCR) revealed miR-103 was highly expressed in GC tissues and cell lines. miR-103 expression was correlated closely with tumor size, Lauren’s classification, and lymph node metastasis. Importantly, Kaplan-Meier analysis revealed that high expression of miR-103 was significantly associated with poor overall survival and disease-free survival of GC patients. Downregulation of miR-103 by transfecting with miR-103 inhibitor significantly suppressed cell proliferation, induced apoptosis, inhibited migration and invasion in vitro and in vivo. Furthermore, miRNA target databases and luciferase reporter assay confirmed that Kruppel-like Factor-4 (KLF4) was a direct target of miR-103 in GC, and there was a significant inverse correlation between miR-103 and KLF4 expression in GC tissues. Moreover, KLF4 downregulation could rescue miR-103’s oncogenic effect on GC cell proliferation, apoptosis, migration, and invasion. Therefore, these results suggested that miR-103 overexpression could contribute to tumor progression by suppressing KLF4, and it might serve as a promising candidate for the prognosis of GC patients.
52 citations
Cites background from "MicroRNA-103 suppresses tumor cell ..."
...Recently, miR-103 has been the focus of many studies and has been shown to function as a oncogen, and be upregulated in several types of cancer such as colorectal cancer [4], endometrial cancer [5], and prostate cancer [6]....
[...]
...Overexpression of miR-103 has been found in several type human cancers and previous studies reported that miR-103 could enhance the proliferation, migration, and invasion of cancer cells by targeting anti-oncogenes DICER and PTEN [4], TIMP-3 [5], PDCD10 [6], KLF4 [11] respectively....
[...]
28 Aug 2018
TL;DR: An update on recent advances in structure and function of these CCM proteins is provided, especially focusing on the signaling cascades involved in CCM pathogenesis and the resultant CCM cellular phenotypes in the past decade.
Abstract: Cerebral cavernous malformations (CCM) are manifested by microvascular lesions characterized by leaky endothelial cells with minimal intervening parenchyma predominantly in the central nervous system predisposed to hemorrhagic stroke, resulting in focal neurological defects Till date, three proteins are implicated in this condition: CCM1 (KRIT1), CCM2 (MGC4607), and CCM3 (PDCD10) These multi-domain proteins form a protein complex via CCM2 that function as a docking site for the CCM signaling complex, which modulates many signaling pathways Defects in the formation of this signaling complex have been shown to affect a wide range of cellular processes including cell-cell contact stability, vascular angiogenesis, oxidative damage protection and multiple biogenic events In this review we provide an update on recent advances in structure and function of these CCM proteins, especially focusing on the signaling cascades involved in CCM pathogenesis and the resultant CCM cellular phenotypes in the past decade
51 citations
TL;DR: Results provide a potential therapeutic target that may downregulate SALL4 in glioma, and suggest that microRNA-103, miR-195, and miB-15b post-transcriptionally downregulated the expression of Sall4 and suppressed gliomas cell growth, migration, and invasion, and increased cell apoptosis.
Abstract: Glioma is the common highly malignant primary brain tumor. However, the molecular pathways that result in the pathogenesis of glioma remain elusive. In this study, we found that microRNA-103 (miR-103), microRNA-195 (miR-195), or microRNA-15b (miR-15b), which all have the same 5′ “seed” miRNA portion and share common binding sites in the SALL4 3′-untranslated region (UTR), were downregulated in glioma tissues and cell lines. These miRNAs suppressed glioma cell proliferation, migration, and invasion, induced cell apoptosis, and decreased the level of the SALL4 protein, but not that of SALL4 mRNA, which was identified as a direct target of all three miRNAs. The caspase-3/7 activity expression in U251 cells overexpressing these miRNAs was rescued during SALL4 upregulation. An obvious inverse correlation was observed between SALL4 and miR-103 or miR-195 expression levels in clinical glioma samples. Moreover, enforced expression of SALL4 stimulated cell proliferation, migration, and invasion. In conclusion, these data suggest that miR-103, miR-195, and miR-15b post-transcriptionally downregulated the expression of SALL4 and suppressed glioma cell growth, migration, and invasion, and increased cell apoptosis. These results provide a potential therapeutic target that may downregulate SALL4 in glioma.
45 citations
References
More filters
TL;DR: A substantial proportion of the worldwide burden of cancer could be prevented through the application of existing cancer control knowledge and by implementing programs for tobacco control, vaccination, and early detection and treatment, as well as public health campaigns promoting physical activity and a healthier dietary intake.
Abstract: The global burden of cancer continues to increase largely because of the aging and growth of the world population alongside an increasing adoption of cancer-causing behaviors, particularly smoking, in economically developing countries. Based on the GLOBOCAN 2008 estimates, about 12.7 million cancer cases and 7.6 million cancer deaths are estimated to have occurred in 2008; of these, 56% of the cases and 64% of the deaths occurred in the economically developing world. Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer death among females, accounting for 23% of the total cancer cases and 14% of the cancer deaths. Lung cancer is the leading cancer site in males, comprising 17% of the total new cancer cases and 23% of the total cancer deaths. Breast cancer is now also the leading cause of cancer death among females in economically developing countries, a shift from the previous decade during which the most common cause of cancer death was cervical cancer. Further, the mortality burden for lung cancer among females in developing countries is as high as the burden for cervical cancer, with each accounting for 11% of the total female cancer deaths. Although overall cancer incidence rates in the developing world are half those seen in the developed world in both sexes, the overall cancer mortality rates are generally similar. Cancer survival tends to be poorer in developing countries, most likely because of a combination of a late stage at diagnosis and limited access to timely and standard treatment. A substantial proportion of the worldwide burden of cancer could be prevented through the application of existing cancer control knowledge and by implementing programs for tobacco control, vaccination (for liver and cervical cancers), and early detection and treatment, as well as public health campaigns promoting physical activity and a healthier dietary intake. Clinicians, public health professionals, and policy makers can play an active role in accelerating the application of such interventions globally.
52,293 citations
TL;DR: The current understanding of miRNA target recognition in animals is outlined and the widespread impact of miRNAs on both the expression and evolution of protein-coding genes is discussed.
18,036 citations
TL;DR: Evidence is mounting that animal miRNAs are more numerous, and their regulatory impact more pervasive, than was previously suspected.
Abstract: MicroRNAs (miRNAs) are small RNAs that regulate the expression of complementary messenger RNAs. Hundreds of miRNA genes have been found in diverse animals, and many of these are phylogenetically conserved. With miRNA roles identified in developmental timing, cell death, cell proliferation, haematopoiesis and patterning of the nervous system, evidence is mounting that animal miRNAs are more numerous, and their regulatory impact more pervasive, than was previously suspected.
9,986 citations
TL;DR: The results indicate that microRNAs are components of the molecular circuitry that controls mouse hematopoiesis and suggest that other micro RNAs have similar regulatory roles during other facets of vertebrate development.
Abstract: MicroRNAs (miRNAs) are an abundant class of ∼22-nucleotide regulatory RNAs found in plants and animals. Some miRNAs of plants, Caenorhabditis elegans, and Drosophila play important gene-regulatory roles during development by pairing to target mRNAs to specify posttranscriptional repression of these messages. We identify three miRNAs that are specifically expressed in hematopoietic cells and show that their expression is dynamically regulated during early hematopoiesis and lineage commitment. One of these miRNAs, miR-181, was preferentially expressed in the B-lymphoid cells of mouse bone marrow, and its ectopic expression in hematopoietic stem/progenitor cells led to an increased fraction of B-lineage cells in both tissue-culture differentiation assays and adult mice. Our results indicate that microRNAs are components of the molecular circuitry that controls mouse hematopoiesis and suggest that other microRNAs have similar regulatory roles during other facets of vertebrate development.
3,307 citations
TL;DR: It is reported that the bantam gene of Drosophila encodes a 21 nucleotide microRNA that promotes tissue growth and identifies the pro-apoptotic gene hid as a target for regulation by bantam miRNA, providing an explanation for bantam's anti-APoptotic activity.
2,063 citations