MicroRNA-34a Inhibits Human Osteosarcoma Proliferation by Downregulating Ether à go-go 1 Expression

Wu, Xinyu; Zhong, Donglai; Gao, Quan; Zhai, Wenliang; Ding, Zhenqi; Wu, Jin

doi:10.7150/ijms.5528

Cited by 77 publications

(66 citation statements)

References 39 publications

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“…miR-34a has been demonstrated to serve tumor promoting or suppressive roles in different types of human cancer (16)(17)(18). For instance, Ma et al (16) reported that miR-34a inhibited the proliferation and promoted the apoptosis of non-small cell lung cancer cells by targeting transforming growth factor β receptor 2.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‑34a directly targets high‑mobility group box 1 and inhibits the cancer cell proliferation, migration and invasion in cutaneous squamous cell carcinoma

Luo

Zhou

et al. 2017

Exp Ther Med

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Abstract. Cutaneous squamous cell carcinoma (CSCC) is the second most common type of skin cancer with increasing incidence. In recent years, several microRNAs (miRs) have been demonstrated to serve an oncogenic or tumor suppressive role in CSCC. However, the exact role of miR-34a in CSCC and the underlying regulatory mechanism remain unclear. The present study aimed to investigate the regulatory mechanism of miR-34a in the malignant phenotypes of CSCC cells using MTT assay, wound healing assay and transwell assay. It was observed that miR-34a was significantly downregulated in CSCC tissues and cell lines, and low miR-34a expression was associated with the aggressive progression of CSCC. Restoration of miR-34a significantly suppressed the proliferation, migration and invasion of CSCC SCL-1 cells. High-mobility group box 1 (HMGB1) was then identified as a target gene of miR-34a in SCL-1 cells using bioinformatics prediction. The expression of HMGB1 was significantly upregulated in the CSCC tissues and cell lines. Furthermore, the protein expression of HMGB1 was negatively regulated by miR-34a in SCL-1 cells, while overexpression of HMGB1 impaired the inhibitory effects of miR-34a on SCL-1 cells. These findings suggest that miR-34a represses the malignant phenotypes of CSCC cells, at least partly, via the inhibition of HMGB1. Therefore, miR-34a may be used as a promising therapeutic candidate for CSCC.

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Section: Discussionmentioning

confidence: 99%

MicroRNA‑34a directly targets high‑mobility group box 1 and inhibits the cancer cell proliferation, migration and invasion in cutaneous squamous cell carcinoma

Luo

Zhou

et al. 2017

Exp Ther Med

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“…Zhang et al (29) demonstrated that miR-34a could regulate mesangial proliferation and glomerular hypertrophy by directly inhibiting GAS1 in early diabetic nephropathy (DN). A further study has ascertained that miR-34a was able to inhibit osteosarcoma growth through the downregulation of Eag1 expression (17). Recently, miR-34a has been shown to be one of the key mediators and downstream factors of p53 (30).…”

Section: Discussionmentioning

confidence: 99%

“…However, the specific role of miRNAs in T2DM has yet to be elucidated. Previous studies have demonstrated that miR-34a directly targets p53 and serves a crucial role in p53-mediated biological processes, such as cell cycle arrest, apoptosis and senescence (17), functioning downstream of the p53 pathway and participating in the initiation and progression of certain types of cancer (18 research has reported that p53 is involved in T cell development (19), which is of note as T cells mediate the immune response and inhibit autoimmune disease (20,21). miR-125b is predicted to be able to bind to B lymphocyte-induced maturation protein-1 (Blimp-1) and interferon regulatory factor-4 (IRF-4) transcription factors, which are essential for plasma cell differentiation (22).…”

Section: Introductionmentioning

confidence: 99%

miR‑34a and miR‑125b are upregulated in peripheral blood mononuclear cells from patients with type 2 diabetes mellitus

Yan-xin

Pan

et al. 2017

Exp Ther Med

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Abstract. Type 2 diabetes mellitus (T2DM) is a leading cause of blindness, non-traumatic amputation and end-stage renal disease, as well as a major cardiovascular risk factor. To determine whether miR-125b and miR-34a serve an important role in the development of T2DM, the current study investigated the expression profile of two microRNAs (miR-34a and miR-125b) and their relative genes in peripheral blood mononuclear cells from 73 patients with T2DM and 52 healthy donors by reverse transcription-quantitative polymerase chain reaction In addition, the association between miR-34a, miR-125b and their relevant genes expression profile were analyzed with respect to the pathogenesis of T2DM. The present study demonstrated that the expression levels of miR-125b and miR-34a were elevated in peripheral blood mononuclear cell samples from patients with T2DM. Furthermore, miR-34a and miR-125b were positively correlated with low-density lipoprotein/high-density lipoprotein (HDL) and Foxp3 and negatively related to triglyceride/HDL. However, no correlation among miR-34a, miR-125b and the value of homeostasis model assessment of insulin resistance, homeostasis model assessment of β-cell function and the genes of B lymphocyte-induced maturation protein-1, interferon regulatory factor-4, P53 and retinoid-related orphan receptor γt were observed. These results indicate that the alteration of miR-34a and miR-125b exists in patients with T2DM, which may be involved in the pathogenesis of T2DM, and could be a potential novel biomarker of T2DM. IntroductionType 2 diabetes mellitus (T2DM), formerly termed non-insulin-dependent diabetes mellitus or adult-onset diabetes, is a multifactor disease that involves complex interactions between genes (1-3), abnormalities of the immune system (4-6), environmental factors (7-10) and health-impacting behavior (11,12), and represents a serious public health problem in numerous developed countries (13). Current investigations have revealed a definite global increase in the incidence and prevalence of diabetes. In 2013, 382 million people worldwide were estimated to be diabetic by the International Diabetes Federation, which is expected to rise to 592 million cases in the year 2035 (14). As a result of the increasing rate of diabetes and its widespread societal and economic consequences, prevention of diabetes among people at high risk is an important public health issue in clinic practice. However, the extent to which multiple defects in the regulation of lipids, insulin secretion and action, and the immune system contribute to the pathogenesis of T2DM has yet to be elucidated.MicroRNAs (miRNAs) are a class of small, single-stranded non-coding RNAs (~22 nucleotides) that are transcribed from the DNA of a gene, and modulate the expression of a network of mRNAs through binding to the 3'-untranslated region (3'-UTR), 5'-UTR or to the open reading frame of target mRNAs (15). Notably, each miRNA is able to target multiple mRNAs. Growing evidence indicates that miRNAs are involved in T2DM (16). However,...

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“…Gene expression profiling studies have revealed that miR expression may be an excellent biomarker for cancer diagnosis and prognosis estimation (Dieckmann et al, 2012;Takahashi et al, 2012). In terms of osteosarcoma, abnormal expression of several miRs such as miR-206 (Bao et al, 2013), miR-34a (Wu et al, 2013), and miR-145 have been reported. Novello et al (2013) found that miR-1 and miR-133b may regulate cell proliferation of osteosarcoma cells (Novello, et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Decreased miR-134 expression and its tumor-suppressive function in human osteosarcoma

Bao

Peng

et al. 2015

Genet. Mol. Res.

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ABSTRACT. Dysregulation of microRNA (miR) is often associated with cancer development and progression. Aberrant expression of miR-134 has been found in some types of cancer. However, its expression and function in osteosarcoma remain unclear. The aim of this study was to explore the effects of miR-134 in osteosarcoma tumorigenesis and development. The expression level of miR-134 was quantified by real-time reverse transcription-polymerase chain reaction in human osteosarcoma cell lines and tissues. The effects of miR-134 on MG-63 cell phenotypes and tumorigenicity in vivo were observed using flow cytometry, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, transwell invasion, migration, and scratch migration assays. MiR-134 was significantly downregulated in osteosarcoma cell lines and clinical specimens. Decreased miR-134 expression was significantly associated with large tumor size, positive distant metastasis, and advanced clinical stage. Low miR-134 expression in osteosarcoma was an independent 16772 Y. Bao et al.©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 14 (4): 16771-16781 (2015) predictor of poor survival. Overexpression of miR-134 inhibited MG-63 cell proliferation, invasion, and migration, promoted cell apoptosis in vitro, and suppressed tumorigenicity in vivo. These findings indicate that miR-134 may act as a tumor suppressor in osteosarcoma and could serve as a novel therapeutic agent for miRNA-based therapy.

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MicroRNA-34a Inhibits Human Osteosarcoma Proliferation by Downregulating Ether à go-go 1 Expression

Cited by 77 publications

References 39 publications

MicroRNA‑34a directly targets high‑mobility group box 1 and inhibits the cancer cell proliferation, migration and invasion in cutaneous squamous cell carcinoma

MicroRNA‑34a directly targets high‑mobility group box 1 and inhibits the cancer cell proliferation, migration and invasion in cutaneous squamous cell carcinoma

miR‑34a and miR‑125b are upregulated in peripheral blood mononuclear cells from patients with type 2 diabetes mellitus

Decreased miR-134 expression and its tumor-suppressive function in human osteosarcoma

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