Numerous microRNAs (miRNAs) are aberrantly expressed in glioma, and implicated in glioma occurrence and development. Therefore, the development of miRNAs as potential therapeutic targets for the treatment of patients with glioma has been proposed. miR‑379 has been shown to be aberrantly expressed in the progression of malignant tumours. However, the expression, biological functions and mechanism of miR‑379 in glioma are yet to be fully understood. Hence, the present study aimed to detect miR‑379 expression, investigate its functional relevance and explore its associated molecular mechanism in glioma. In this study, miR‑379 expression was significantly downregulated in glioma tissues and cell lines. Enforced miR‑379 expression markedly suppressed the cell proliferation and invasion of glioma. Metadherin (MTDH) was identified as a direct target of miR‑379 in glioma. The miR‑379 expression and MTDH mRNA levels exhibited an inverse association in glioma tissues. The restoration of the MTDH expression partially rescued the inhibitory effects of miR‑379 overexpression on glioma cell proliferation and invasion, and the upregulation of miR‑379 inhibited the activation of phosphatase and tensin homolog (PTEN)/AKT serine/threonine kinase (AKT) signaling pathway. Overall, these findings demonstrated that miR‑379 may play tumour‑suppressing roles in glioma through downregulation of MTDH and regulation of the PTEN/AKT signaling pathway, suggesting that miR‑379 might be a possible target for the treatment of patients with this malignancy.

Apoptosis, one of the major causes of podocyte loss, has been reported to have a vital role in diabetic nephropathy (DN) pathogenesis, and understanding the mechanisms underlying the regulation of podocyte apoptosis is crucial. Metadherin (MTDH) is an important oncogene, which is overexpressed in most cancers and responsible for apoptosis, metastasis, and poor patient survival. Here we show that the expression levels of Mtdh and phosphorylated p38 mitogen-activated protein kinase (MAPK) are significantly increased, whereas those of the microRNA-30 family members (miR-30s) are considerably reduced in the glomeruli of DN rat model and in high glucose (HG)-induced conditionally immortalized mouse podocytes (MPC5). These levels are positively correlated with podocyte apoptosis rate. The inhibition of Mtdh expression, using small interfering RNA, but not Mtdh overexpression, was shown to inhibit HG-induced MPC5 apoptosis and p38 MAPK pathway, and Bax and cleaved caspase 3 expression. This was shown to be similar to the effects of p38 MAPK inhibitor (SB203580). Furthermore, luciferase assay results demonstrated that Mtdh represents the target of miR-30s. Transient transfection experiments, using miR-30 microRNA (miRNA) inhibitors, led to the increase in Mtdh expression and induced the apoptosis of MPC5, whereas the treatment with miR-30 miRNA mimics led to the reduction in Mtdh expression and apoptosis of HG-induced MPC5 cells in comparison with their respective controls. Our results demonstrate that Mtdh is a potent modulator of podocyte apoptosis, and that it represents the target of miR-30 miRNAs, facilitating podocyte apoptosis through the activation of HG-induced p38 MAPK-dependent pathway.

Colorectal and lung cancers account for one-third of all cancer-related deaths worldwide. Previous studies suggested that Metadherin (MTDH) is involved in the development of colorectal and lung cancers. However, how MTDH regulates the pathogenesis of these cancers remains largely unknown. Using genetically modified mouse models of spontaneous colorectal and lung cancers, we found that MTDH promotes cancer progression by facilitating Wnt activation and by inducing cytotoxic T cell exhaustion, respectively. Moreover, we developed locked nucleic acid-modified (LNA) MTDH antisense oligonucleotides (ASOs) that effectively and specifically suppress MTDH expression in vitro and in vivo. Treatments with MTDH ASOs in mouse models significantly attenuated progression and metastasis of colorectal, lung, and breast cancers. Our study opens a new avenue for developing therapies against colorectal and lung cancers by targeting MTDH using LNA-modified ASO.

Metadherin (MTDH) is identified as an oncogene in multiple cancers including breast cancer, bladder cancer and endometrial cancer. However, the function of MTDH in multiple myeloma (MM) is still unexplored. In this study, we disclose that MTDH is an oncogene in MM. This is characterized by an elevation mRNA level of MTDH and chromosomal gain of MTDH locus in MM cells compared to normal samples. Moreover, MTDH expression significantly increased in MMSET translocation (MS) subgroup, one of the high-risk subgroups in MM, and was significantly correlated with MM patients' poor outcomes in Total Therapy 2 (TT2) cohort. Further knockdown of MTDH expression by shRNA in MM cells induced cell apoptosis, inhibited MM cells growth in vitro and decreased xenograft tumor formation in vivo. Interestingly, opposite to TT2, MM patients with high-MTDH expression showed favorable survival outcomes in the TT3 cohort, while Bortezomib treatment was the major difference between TT2 and TT3 cohort. Furthermore we proved that Bortezomib suppressed pre- and post-transcription levels of MTDH expression of MM cells in vitro and in vivo. Finally, our studies demonstrated that MTDH is a transcriptional gene of MMSET/NFκB /MYC signaling in MM cells, which is inhibited by Bortezomib treatment.

Gastric cancer (GC) is one of the most common and fatal types of cancers worldwide and the specific mechanism has not been completely elucidated. microRNA (miR)‑3664‑5P has rarely been studied and the aim of the present study was to assess an association between miR‑3664‑5P and GC. Differences in miR‑3664‑5P expression in 100 GC (0.1846±0.08276) and paired normal tissues (0.4382±0.1595) were detected using reverse transcription‑quantitative polymerase chain reaction assays (P<0.001). 5‑Ethynyl‑2‑deoxyuridine, Cell Counting Kit‑8, transwell and flow cytometry assays were performed in vitro and the results were further verified using a mouse xenotransplantation and a lung metastasis model in vivo. miR‑3664‑5P was significantly downregulated in GC tissues when compared with normal tissues and positively associated with the prognosis of patients with GC (P<0.001). Overexpression of miR‑3664‑5P suppressed and miR‑3664‑5P knockdown promoted the proliferation and metastasis of GC cells in vitro and in vivo. Following the application of bioinformatic algorithms and luciferase reporter assays, metadherin (MTDH) was confirmed as the target gene of miR‑3664‑5P. miR‑3664‑5P reduced MTDH expression and downregulated the nuclear factor (NF)‑κB signaling pathway. Rescue experiments demonstrated that suppression of MTDH restored the effect of miR‑3664‑5P inhibitors on GC cell lines. The results suggested that miR‑3664‑5P suppressed the proliferation and metastasis of GC cells by attenuating the NF‑κB signaling pathway via MTDH targeting. Consequently, miR‑3664‑5P may have potential to be an independent prognostic factor and biomarker in GC.

microRNA (miR)-22 has been reported to be downregulated in hepatocellular, lung, colorectal, ovarian and breast cancer, acting as a tumor suppressor. The present study investigated the potential effects of miR-22 on gastric cancer invasion and metastasis and the molecular mechanism. miR-22 expression was examined in tumor tissues of in 89 gastric cancer patients by in situ hybridization (ISH) analysis. Additionally, the association between miR-22 levels and clinicopathological parameters was analyzed. A luciferase assay was conducted for target identification. The ability of invasion and metastasis of gastric cancer cells in vitro and in vivo was evaluated by cell migration and invasion assays and in a xenograft model. The results showed that miR-22 was downregulated in the gastric cancer specimens and significantly correlated with the advanced clinical stage and lymph node metastasis. In addition, metadherin (MTDH) was shown to be a direct target of miR-22 and the expression of MTDH was inversely correlated with miR-22 expression in gastric cancer. Ectopic expression of miR-22 suppressed cell invasion and metastasis in vitro and in vivo. The present study suggested that miR-22 may be a valuable prognostic factor in gastric cancer. miR-22 inhibited gastric cancer cell invasion and metastasis by directly targeting MTDH. The novel miR-22/MTDH link confirmed in the present study provided a novel, potential therapeutic target for the treatment of gastric cancer.

Hepatocellular carcinoma (HCC) has frequent incidence and the third highest mortality rate among cancers in the world. This study aimed to clarify the roles of miR-217 and metadherin (MTDH) in HCC. First, we identified that miR-217 expression was downregulated and MTDH expression was upregulated in the HCC tissues. Functional studies revealed that miR-217 negatively regulated MTDH expression via binding to the 3'-untranslated region of MTDH mRNA in the HCC cells. In our further studies, the miR-217 overexpression resulted in downregulation of MTDH expression in HCC cells. The miR-217 overexpression in HCC cells suppressed proliferation, migration, and invasion inducing apoptosis. Taken together, our study provides the initial evidence that the increase of MTDH expression is associated with the decrease of miR-217 expression in HCC. This study also suggests that miR-217 inhibits malignant progression of HCC in vitro and may be used for miRNA-based therapy, possibly via directly targeting MTDH.

Colorectal cancer (CRC) is the third most common malignant disease in men and the second in women worldwide. CRC relapse occurs mostly in liver and lungs, decreasing the 5-year survival to 6 %. Metadherin (MTDH) is overexpressed in several types of cancer, has been implicated in proliferation, invasion, metastasis, angiogenesis, and chemoresistance, and is a factor of poor prognosis in CRC. In this work we addressed the prognostic significance of MTDH expression in CRC progression to the lungs. We found that MTDH gene was more frequently amplified (copy number >1.8) in patients with CRC and relapse to the lung, when compared to patients without lung metastases (17.4 vs 100 %; p < 0.001). We observed a correlation between MTDH gene copy number and MTDH expression by IHC (p = 0.0001). Next we also analyzed MTDH expression by IHC in samples from 85 patients diagnosed with CRC, stage II or III, M0, with at least 3 years of follow-up. Kaplan-Meier survival analysis showed that lung relapse-free survival (HR 5.29, 95 % CI 1.90-14.77, p = 0.0004), liver relapse-free survival (HR 8.59, 95 % CI 0.99-74.18, p = 0.003), relapse-free survival (HR 4.85, 95 % CI 1.88-12.45, p = 0.0003) and overall survival (HR 3.75, 95 % CI 1.15-12.18, p = 0.018) were significantly lower in the group with high MTDH expression. Multivariate analysis showed that high MTDH expression was an independent factor for all outcomes. This study demonstrates that high MTDH expression is a biomarker of relapse in CRC, including lung-specific relapse. Determination of MTDH expression in primary CRC may be useful in the earlier detection of lung metastases in patients with high expression and increased risk.

Prognostication of non-small cell lung cancer is principally based on stage, age and performance status. This review provides an overview of 342 potential prognostic biomarkers in non-small cell lung cancer described between January 2008 and June 2013, evaluating the association between immunohistochemical protein expression and survival endpoint. Numerous studies proposed prognostic biomarkers, but many were only evaluated in a single patient cohort, and a large number of biomarkers revealed inconclusive findings when analyzed in more than one study. Only 26 proteins first described after 2008 (ALDH1A1, ANXA1, BCAR1, CLDN1, EIF4E, EZH2, FOLR1, FOXM1, IL7R, IL12RB2, KIAA1524, CRMP1, LOX, MCM7, MTA1, MTDH, NCOA3, NDRG2, NEDD9, NES, PBK, PPM1D, SIRT1, SLC7A5, SQSTM1 and WNT1) demonstrated a consistent prognostic association in two or more independent patient cohorts, thus qualifying as promising candidates for diagnostic use. Raised quality standards for study design and antibody validation, and integration of preclinical findings with clinical needs are clearly warranted.

Metadherin (MTDH) is involved in aberrant proliferation, migration, and chemoresistance of tumor cells. It has been demonstrated that it can promote tumor growth by modulation multiple oncogenic signaling pathways. However, MTDH expression, significance, and related mechanism in chronic lymphocytic leukemia (CLL) are still unclear. The objective of this study was to investigate the expression of MTDH in CLL and the involvement of Wnt/β-catenin signaling pathway in MTDH effects. Overexpression of MTDH mRNAs was seen in CLL samples. MTDH expression was associated with Rai stage classification of CLL, and altered levels of β2-MG and lactate dehydrogenase in serum samples from patients. Overexpression of MTDH protein was seen in 87 % of CLL samples. Specific siRNAs inhibited MEC-1 cell growth and enhanced cell apoptosis (P < 0.05). Inhibition of MTDH expression resulted in decreased expression levels of lymphoid enhancer-binding factor 1 (LEF-1), and its downstream target genes c-myc and cyclin D1. And there was a strong correlation between MTDH and LEF-1 protein expression in 14 patients with CLL. The results demonstrate that MTDH is specifically expressed in B cell of CLL and exert a preservative role through activation of Wnt signaling pathway. Our findings indicated that MTDH may be a potential therapeutic target of CLL.

Recent studies found that metadherin (MTDH) played an essential role in hepatocellular carcinoma (HCC). Nevertheless, the exact function of MTDH in the pathogenesis of HCC was unclarified. In the present study, we aimed to investigate the clinical significance of MTDH in HCC and its effect on HCC cells. Immunohistochemistry (IHC) was performed to detect MTDH expression in HCC tissues. Data from The Cancer Genome Atlas (TCGA) and ONCOMINE was obtained to examine MTDH expression in HCC and its clinical significance. Meta-analysis was conducted to assess the correlation between MTDH expression and both the prognosis (Overall Survival (OS) or Disease-free Survival (DFS)) and clinicopathological features of HCC via STATA 12.0. In vitro experiments were performed to investigate the role of MTDH in cell growth, caspase-3/7 activity and apoptosis in HCC cells. The MTDH staining was remarkably stronger in HCC tissues than in non-cancer tissues from IHC, TCGA and ONCOMINE data. Moreover, MTDH-positive expression was significantly correlated with pathological grade, distant metastasis and hepatitis B virus (HBV) infection by IHC. For meta-analysis, MTDH expression was indicative of poor OS without heterogeneity in HCC patients. Additionally, MTDH expression was correlated with high-grade histological differentiation, non-vascular invasion and metastasis in HCC. In vitro experiments revealed that MTDH could the inhibit cell growth and activate caspase-3/7 activity and apoptosis in the four HCC cell lines. In conclusion, MTDH expression may serve as a novel targeting strategy for HCC due to its clinical significance and oncogenic function in HCC cells.

Astrocyte elevated gene-1 (AEG-1), also known as MTDH and Lyric, is a novel gene that was first cloned by subtraction hybridization in 2002 and has recently been shown to play a role as a crucial oncogene that acts as a promoter of tumor malignancy. Overexpression and inhibition studies both in in vitro and in vivo models have partly shown the oncogenic roles of AEG-1 in a number of crucial aspects of tumor development and progression, including transformation, evasion of apoptosis, proliferation, cell survival, migration, invasion, metastasis, angiogenesis and chemoresistance through the activation of numerous signaling pathways, such as the nuclear factor κB, PI3K/AKT, Wnt/β-catenin and mitogen-activated protein kinase signaling pathways. However the potential roles of AEG-1, particularly in specific organs or tissues, such as breast tissue, require further clarification. Studies have found that in normal human breast tissue, AEG-1 is always expressed at low levels or is absent, while it is widely overexpressed in many breast cancer cell lines and breast tumors. The present review evaluates the current literature with regards to AEG-1 relative to breast cancer development and progression and highlights new perspectives relative to this molecule, indicating its potential to become a new target for the clinical treatment of breast cancer.

BACKGROUND

Considerable evidence suggests that metadherin (MTDH) is a potentially crucial mediator of tumor malignancy and an important therapeutic target for simultaneously enhancing chemotherapy efficacy and reducing metastasis risk. Inhibition of MTDH expression by RNA interference has been shown in several previous research, but silencing MTDH expression by microRNA (miRNA) interference in breast cancer has not been established. In the present study, we investigated the role of MTDH-miRNA in down-regulation of proliferation, motility and migration of breast carcinoma cells.

METHODS

Expression vectors of recombinant plasmids expressing artificial MTDH miRNA were constructed and transfected to knockdown MTDH expression in MDA-MB-231 breast cancer cells. Expression of MTDH mRNA and protein was detected by RT-PCR and Western blot, respectively. MTT assays were conducted to determine proliferation, and wound healing assays and transwell migration experiments for cell motility and migration.

RESULTS

Transfection of recombinant a plasmid of pcDNA-MTDH-miR-4 significantly suppressed the MTDH mRNA and protein levels more than 69% in MDA-MB-231 breast cancer cells. This knockdown significantly inhibited proliferation, motility and migration as compared with controls.

CONCLUSIONS

MTDH-miRNA may play an important role in down- regulating proliferation, motility and migration in breast cancer cells, and should be considered as a potential small molecule inhibitor therapeutic targeting strategy for the future.

In this study, one homogeneous polysaccharide (SP1), with a molecular weight of 56kDa, was isolated from the Huaier fruiting bodies. It had a backbone consisting of 1,4-linked-β-d-Galp and 1,3,6-linked-β-d-Galp residues, which was terminated with 1-linked-α-d-Glcp and 1-linked-α-l-Araf terminal at O-3 position of 1,3,6-linked-β-d-Galp unit along the main chain in the ratio of 1.1:2.0:1.1:1.1. MTT assay showed that shMTDH or SP1 (100, 200 and 400μg/ml) was able to suppress the proliferation of MCF-7 cells, due to a significant increase in the number of apoptotic cells as determined by flow cytometric analysis. Furthermore, Western blot analysis revealed that SP1 or shMTDH treatment led to a rise of ratio between proapoptotic Bax and antiapoptotic Bcl-2 protein in MCF-7 cells. In addition, carcinogene MTDH protein expression in MCF-7 cells received SP1 (100, 200 and 400μg/mL) or shMTDH treatment was also repressed after 48h incubation. Taken together, these findings indicated that SP1 has anticancer potential in the treatment of human breast cancer.

Multiple myeloma (MM) is a hematological tumor and is characterized by the infiltration of malignant clonal plasma cells (PCs) in bone marrow. MicroRNAs (miRNAs or miRs) have been reported to play an important role in the genesis and progression of MM. However, little is known about the clinical diagnostic value and biological functions of miR-30d in MM. In this study, to investigate the role of miR-30d in MM, we used reverse transcription-quantitative polymerase chain reaction quantitative (RT-qPCR) to detect the relative expression level of miR-30d in the serum of 81 patients with primary MM and 78 healthy donors (HDs). The biological functions of miR-30d were then assessed by CCK-8 assay, flow cytometric analysis of apoptosis and western blot (WB) analysis in U266 cells. Moreover, the confirmation of the target gene of miR-30d was conducted by luciferase reporter assay. Our results indicated that miR-30d expression was significantly downregulated in the serum of patients with primary MM compared with that of the HDs and that it was significantly associated with several clinical indicators of MM. Further cell functional analyses using the U266 cells revealed that miR-30d functions as a tumor suppressor gene in MM by inhibiting cell viability and promoting cell apoptosis. Moreover, miR-30d was confirmed to directly bind to the 3'UTR of its target gene, metadherin (MTDH) and inhibit the activation of the downstream PI3K/Akt signaling pathway. On the whole, the findings of this study indicate that the serum expression level of miR-30d is of great significance to the diagnosis and treatment monitoring of patients with MM. Moreover, miR-30d carries out its antitumor role in U266 cells through the inhibition of the activation of the PI3K/Akt signaling pathway by negatively regulating MTDH, which reveals its potential for use as a therapeutic target for MM.

Hypoxia is a hallmark of progressive cancer. Hypoxic cancer cells trigger glycolysis in response to a decreased O2 supply to meet metabolic and bioenergetic demands. Meanwhile, these responses to hypoxia and alterations of the microenvironment promote cancer cell metastasis by increasing transcription of hypoxia-inducible factor (HIF)-regulated genes. However, the detailed mechanism by which hypoxia regulates cancer cell metastasis and glycolysis remains to be investigated. In the present study, we identified that metadherin (MTDH), a multifaceted oncogene, is involved in the regulation of head and neck squamous cell carcinoma (HNSCC) metastasis and invasion under hypoxic conditions. Furthermore, the study indicated that there is a positive feedback loop between HIF-1α and MTDH in HNSCC cells, and that hypoxia promotes HNSCC cell metastasis and epithelial-mesenchymal transition by mediating the HIF-1α-MTDH loop. These findings implicate HIF-1α-MTDH as a promising target for anticancer drugs in solid tumors, and help to explain the pro-tumorigenic and unfavorable effect of MTDH on HNSCC observed in our previous studies.

Metadherin (MTDH) was first identified in primary human fetal astrocytes exposed to HIV-1 in 2002 and then recognized as an important oncogene mediating tumorigenesis, progression, invasiveness, and metastasis of carcinomas. Epithelial-mesenchymal transition (EMT) is a vital process in embryonic development, organ repair, and cancer progression. MTDH and EMT have also been proved to be related to the prognosis of patients with cancers. Recent studies reveal a relationship between MTDH overexpression and EMT in some malignancies. This review highlights the overexpression of MTDH and EMT in cancers and their correlations in clinical studies. Positive correlations have been established between MTDH and mesenchymal biomarkers, and negative correlations between MTDH and epithelial biomarkers have also been established. Furthermore, experiments reveal EMT regulated by MTDH, and some signal pathways have been established. Some anticancer drugs targeting MTDH and EMT are introduced in this review. Some perspectives concerning EMT regulation by MTDH are also presented in this review.

Metadherin (MTDH), a novel oncoprotein, has been implicated in the carcinogenesis in various aspects of tumor malignancy. Overexpression of the MTDH promotes the survival and proliferation of lung cancer cells. Agent that can suppress MTDH activation would have potential to be developed for cancer therapeutics. In this study, we investigated the antitumor effect of evodiamine in human non-small-cell lung carcinoma (NSCLC) A549 cell line and the inhibitory effect of evodiamine on MTDH pathway. 3-(4,5-Dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and annexin V/propidium iodide (PI) staining assays demonstrated that evodiamine or MTDH short hairpin RNA (shRNA) significantly inhibited proliferation of A549 cells via induction of apoptosis. Besides, evodiamine or MTDH shRNA-induced activation of the caspase-3 in A549 cells under same conditions. In addition, Western blotting analysis showed that treatment of A549 cells with evodiamine or MTDH shRNA resulted in an increase of proapoptotic protein Bax expression but decreased the expression levels of antiapoptotic protein Bcl-2 and MTDH, which altogether account for apoptotic cell death. Taken together, our results suggest that the evodiamine suppress the proliferation of lung cancer cells, at least, in part, via inhibition of MTDH expression and activation of apoptosis.

The present study aimed to explore the effects of microRNA (miRNA)‑30a‑5p on tumor proliferation and to seek a potential therapeutic target for the treatment of human renal cancer. The results demonstrated that the expression levels of miRNA‑30a‑5p were reduced in tumor samples from patients with renal cancer compared with in normal tissue samples. Overall survival and disease‑free survival were increased in patients with renal cancer and high miRNA‑30a‑5p expression compared with in those with low miRNA‑30a‑5p. Furthermore, overexpression of miRNA‑30a‑5p suppressed cell proliferation, induced apoptosis, and promoted caspase‑3/9 activities and B‑cell lymphoma 2‑associated X protein (Bax) protein expression in Caki‑2 cells. In addition, the results confirmed that overexpression of miRNA‑30a‑5p inhibited metadherin (MTDH), upregulated phosphatase and tensin homolog (PTEN) and suppressed phosphorylated (p)‑protein kinase B (AKT) protein expression levels in Caki‑2 cells. Furthermore, transfection with small interfering RNA‑MTDH, increased the effects of miRNA‑30a‑5p on the inhibition of cell proliferation, and promotion of apoptosis, caspase‑3/9 activities and Bax protein expression levels in Caki‑2 cells. Knockdown of MTDH expression also upregulated PTEN and suppressed p‑AKT protein expression in Caki‑2 cells. In conclusion, the present study is the first, to the best of our knowledge, to provide evidence suggesting that miRNA‑30a‑5p suppresses tumor human renal cancer cell proliferation via the MTDH/PTEN/AKT pathway.

Glioma is the most common and aggressive type of primary malignant brain tumour. Increasing evidence has revealed that microRNAs play important roles in multiple biological processes related to glioma occurrence, development, diagnosis, treatment and prognosis. MicroRNA-202 (miR-202) has been studied in several types of human cancer, whereas the biological roles of miR-202 in glioma remain unknown. The present study, aimed to investigate the expression, clinical significance and biological roles of miR-202 in glioma, as well as its underlying molecular mechanism. We found that miR-202 was significantly downregulated in glioma tissues and cell lines. Low miR-202 expression was associated with Karnofsky performance status (KPS) score and World Health Organization (WHO) grade of glioma patients. Functional assays revealed that ectopic expression of miR-202 inhibited cell proliferation, migration and invasion of glioma. In addition, metadherin (MTDH) was identified as a direct target gene of miR-202 in glioma through bioinformatic analysis, luciferase reporter assay, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting. Furthermore, MTDH expression was upregulated and negatively correlated with miR-202 expression in clinical glioma tissues. MTDH knockdown had similar roles to miR-202 overexpression in glioma cells. Rescue experiments revealed that upregulation of MTDH reversed the suppression of glioma cell growth and metastasis by miR-202. Moreover, miR-202 impaired the PI3K/Akt and Wnt/β-catenin pathways. These results highlight the tumour-suppressive effect of miR-202 in glioma, thereby suggesting that miR-202 may be a potential therapeutic target for the treatment of patients with this malignancy.

UNASSIGNED

MicroRNAs (miRNAs) have been reported to play crucial roles in multiple cancers including non-small cell lung cancer (NSCLC). Here, we investigated the role of miR-145 and miR-497 in TGF-β-induced epithelial-mesenchymal transition (EMT) process of NSCLC.

UNASSIGNED

We performed quantitative real time PCR (qRT-PCR) to detect the expression level of miR-145 and miR-497 in NSCLC cell lines. Then in the presence/absence of TGF-β, we transfected miRNA mimics or inhibitor into A549 and H1299 cells and investigated the role of miR-145 and miR-497 in cell migration and invasion using transwell and wound-healing assay. The regulation role of miR-145 and miR-497 on Metadherin (MTDH) was determined by luciferase assay. The expression level of MTDH and EMT markers E-cadherin and vimentin were detected on mRNA and protein level.

UNASSIGNED

In our study, our results showed that miR-145 and miR-497 were downregulated in NSCLC cell lines. Overexpression of miR-145 and miR-497 inhibited TGF-β-induced EMT and suppressed cancer cell migration and invasion, while the opposite results were observed in cells transfected with miR-145 or miR-497 inhibitor. Moreover, the luciferase assay confirmed that miR-145 and miR-497 attenuated MTDH expression by directly binding 3'-UTR of MTDH mRNA and exert the tumor-suppression role.

UNASSIGNED

Overall, we demonstrated that miR-145 and miR-497 functioned as EMT-suppressor in NSCLC by targeting MTDH, provided new evidence that miR-145 and miR-497 as potential therapeutic targets.