MicroRNA-34a targets notch1 and inhibits cell proliferation in glioblastoma multiforme
77
Citation
0
Reference
10
Related Paper
Citation Trend
Abstract:
Aberrant expression of microRNAs (miRNAs) has been implicated in cancer initiation and progression. In this study, we found that microRNA-34a (miR-34a) is significantly downregulated in glioblastoma multiforme (GBM) specimens compared with normal brain tissues. Growth curve and colony formation assays revealed that miR-34a suppresses proliferation of U373MG and SHG44 glioblastoma cells. Overexpression of miR-34a could induce apoptosis of glioblastoma cells. Also, we identified notch1 as a direct target gene of miR-34a. Knockdown of notch1 showed similar cellular functions as overexpression of miR-34a both in vitro and in vivo. Collectively, our findings show that miR-34a is downregulated in GBM cells and inhibits GBM growth by targeting notch1.Keywords:
U87
Aberrantly expressed microRNAs (miRNAs/miRs) and their role in cancer development have recently gained more attention. However, the potential role of miRNAs in hepatocellular carcinoma (HCC) remains largely unknown. In this study, we demonstrated that miR-377 was markedly downregulated in HCC cell lines and primary human HCC tissues. The decreased expression of miR-377 contributes to the upregulation of Bcl-xL expression by targeting its 3-untranslated region (3-UTR). Functionally, knockdown of miR-377 noticeably increased HCC cell growth and colony formation and inhibited apoptosis. In contrast, overexpression of miR-377 suppressed cell proliferation and increased apoptosis. This study provides new insights for the use of miR-377 as a potential molecular target in HCC therapy.
Cite
Citations (20)
LncRNA SNHG4 has been reported to be an oncogenic lncRNA in osteosarcoma. Our preliminary analysis of the cancer genome atlas dataset revealed the upregulation of SNHG4 in glioblastoma (GBM). In this study, we confirmed the upregulation of SNHG4 in GBM tissues collected from GBM patients. In addition, lower survival rate of GBM patients was observed in patients with high SNHG4 expression level. SNHG4 can directly interact with miR-138, while SNHG4 expression was no altered after miR-138 overexpression. Interestingly, SNHG4 overexpression led to the upregulation of c-Met, a target of miR-138. Cell counting kit-8 assay showed that miR-138 overexpression resulted in decreased proliferation rate of GBM cells. SNHG4 and c-Met overexpression played opposite roles and reduced the effects of miR-138. Therefore, SNHG4 regulates miR-138/c-Met axis to promote the proliferation of GBM cells.
U87
Cite
Citations (13)
Abstract Background: ZNF674-AS1, a recently characterized long noncoding RNA, shows prognostic significance in hepatocellualar carcinoma and glioma. However, the expression and function of ZNF674-AS1 in non-small cell lung cancer (NSCLC) is unclear. Methods: In this work, we investigated the expression of ZNF674-AS1 in 83 pairs of NSCLC specimens and adjacent noncancerous lung tissues. The clinical significance of ZNF674-AS1 in NSCLC was analyzed. The role of ZNF674-AS1 in NSCLC growth and cell cycle progression was explored. Results: Our data show that ZNF674-AS1 expression is decreased in NSCLC compared to normal tissues. ZNF674-AS1 downregulation is significantly correlated with advanced TNM stage and decreased overall survival of NSCLC patients. Overexpression of ZNF674-AS1 inhibits NSCLC cell proliferation, colony formation, and tumorigenesis, which is accompanied by a G0/G1 cell cycle arrest. Conversely, knockdown of ZNF674-AS1 enhances the proliferation and colony formation of NSCLC cells. Biochemically, ZNF674-AS1 overexpression increases the expression of p21 through downregulation of miR-423-3p. Knockdown of p21 or overexpression of miR-423-3p blocks ZNF674-AS1-mediated growth suppression and G0/G1 cell cycle arrest. In addition, ZNF674-AS1 expression is negatively correlated with miR-423-3p in NSCLC specimens. Conclusions: ZNF674-AS1 suppresses NSCLC growth by downregulating miR-423-3p and inducing p21. This work suggests the therapeutic potential of ZNF674-AS1 in the treatment of NSCLC.
Cite
Citations (0)
Long non-coding RNAs (lncRNAs) are critical drivers and suppressors of human hepatocellular carcinoma (HCC). The downregulation of transmembrane protein 220 antisense RNA 1 (TMEM220-AS1) is correlated with poor prognosis in HCC. Nevertheless, the role of TMEM220-AS1 in HCC and the underlying mechanism remains unclear. In this study, TMEM220-AS1 levels were markedly reduced in HCC tissues compared with noncancerous tissues. TMEM220-AS1 downregulation was confirmed in HCC cell lines. TMEM220-AS1 expression was associated with tumor stage, venous infiltration, tumor size, and survival of HCC patients. TMEM220-AS1 overexpression suppressed the migration, invasion, and proliferation of HCC cells. Interestingly, ectopic expression of TMEM220-AS1 increased TMEM220 levels in HCC cells. Decreased TMEM220 levels were observed in HCC tissues and cell lines. TMEM220 expression was positively correlated with TMEM220-AS1 levels in HCC tissue samples and TMEM220 downregulation was significantly correlated with reduced patient survival. TMEM220 overexpression suppressed HCC cell proliferation and mobility. TMEM220 knockdown eliminated the suppressive effect of TMEM220-AS1 in HCCLM3 cells. Mechanistically, TMEM220 overexpression reduced the nuclear accumulation of β-catenin and decreased MYC, Cyclin D1, and Snail1 mRNA levels in HCCLM3 cells. BIO, a GSK3β inhibitor, eliminated TMEM220-induced Wnt/β-catenin pathway inactivation and inhibited HCC cell proliferation and mobility. In conclusion, TMEM220-AS1 and TMEM220 were expressed at low levels in HCC patients. TMEM220-AS1 inhibited the malignant behavior of HCC cells by enhancing TMEM220 expression and subsequently inactivating the Wnt/β-catenin pathway.
Ectopic expression
Cite
Citations (7)
In this study, we found miR-362-5p was upregulated in bladder cancer tissues and we predicted that QKI is potential a target of miR-362-5p and MBNL1-AS1 might be able to directly bind with miR-362-5p. We attempted to evaluate whether miR-362-5p could play its roles in bladder cancer through regulating QKI (quaking) and whether the expression and function of miR-362-5p could be mediated by lncRNA MBNL1-AS1. We performed the gain- and loss- function experiments to explore the association between miR-362-5p expression and bladder cancer proliferation. In vivo, the nude mice were injected with miR-362-5p knockdown SW780 cells to assess the effects of miR-362-5p on tumor growth. The results showed upregulation of miR-362-5p promoted cell proliferation of bladder cancer cells. MBNL1-AS1 and QKI could directly bind with miR-362-5p, and knockdown of MBNL1-AS1 or QKI could abrogate the regulatory effects of miR-362-5p on bladder cancer cell proliferation. Furthermore, downregulation of miR-362-5p inhibited bladder tumor growth and increased QKI expression. Our data unveiled that miR-362-5p may play an oncogenic role in bladder cancer through QKI and MBNL1-AS1 might function as a sponge to mediate the miR-362-5p expression and function.
Cite
Citations (21)
Temozolomide
U87
Cite
Citations (13)
Glioblastoma multiforme (GBM) is the most common and aggressive form of brain cancer. Evidences have suggested that CD133 is a marker for a subset of glioblastoma cancer stem cells. However, whether miRNA plays a critical role in CD133 + GBM is poorly understood. Here, we identified that miR‐154 was upregulated in CD133 + GBM cell lines. Knockdown of miR‐154 remarkably suppressed proliferation and migration of CD133 + GBM cells. Further study found that PRPS1 was a direct target of miR‐154 in CD133 + GBM cells. Overexpression of PRPS1 exhibited similar effects as miR‐154 knockdown in CD133 + GBMs. Our study identified miR‐154 as a previously unrecognized positive regulator of proliferation and migration in CD133 + GBM cells and a potentially therapeutic target of GBMs. Copyright © 2016 John Wiley & Sons, Ltd.
Cite
Citations (16)
Abstract Glioblastoma (GBM) is the most common malignancy tumor of central nervous system. PTBP3 was closely associated with the development of tumor. However, the function and mechanism of PTBP3 in GBM is little known. We found that PTBP3 was upregulated in GBM, and higher expression of PTBP3 corrected with the poor survival of GBM patients. Knockdown PTBP3 reduced proliferation, EMT, invasion, and migration of GBM. Conversely, overexpressing PTBP3 has an opposite effect. Moreover, we found that PTBP3 stabilized Twist1 by decreasing its ubiquitination and degradation. Furthermore, orthotopic xenograft models were used to demonstrate the PTBP3 on the development of GBM in vivo . This study proved that PTBP3 promoted tumorigenesis of GBM by stabilizing Twist1, which provided a new therapeutic target for GBM.
Cite
Citations (0)
In recent years, changes in microRNA (miRNA) expression have been detected in almost all human cancer types, including glioblastoma (GBM). Dysregulation of miRNAs may play tumor-suppressing or oncogenic roles in the initiation and progression of GBM, and may be involved in the regulation of multiple pathological behaviors. Therefore, identifying the clinical value and functional role of GBM-related miRNAs may provide effective therapeutic targets for the treatment of patients with this fatal malignancy. Dysregulation of miR-744 has been identified in several human cancer types. However, to the best of our knowledge, little is known concerning the expression pattern and biological roles of miR-744 in GBM. In this study, we found that miR-744 was significantly downregulated in GBM tissues and cell lines. Decreased miR-744 expression was significantly correlated with the Karnofsky Performance Scale (KPS) and World Health Organization (WHO) grade in GBM patients. miR-744 upregulation inhibited the proliferation, colony formation, migration, and invasion, in addition to inducing apoptosis of GBM cells in vitro. Inhibition of miR-744 had the opposite effect on these behaviors in GBM cells. Additionally, miR-744 attenuated the tumor growth of GBM cells in vivo. Furthermore, NIN1/RPN12 binding protein1 homolog (NOB1) was identified as a direct target gene of miR-744 in GBM cells. NOB1 was confirmed to be upregulated in GBM tissues, and this was inversely correlated with upregulation of miR-744 expression. Moreover, NOB1 knockdown exhibited similar inhibitory effects as miR-744 overexpression in GBM cells. Notably, recovered NOB1 expression counteracted the tumor-suppressing roles of miR-744 in the malignant phenotypes of GBM cells. Taken together, these results demonstrate that miR-744 directly targets NOB1 to inhibit the aggressive behaviors of GBM cells. Hence, the miR-744/NOB1 axis may be useful in the identification of novel therapies for GBM patients.
U87
Cite
Citations (18)
Upregulated gene 11 (URG11), a new gene upregulated by hepatitis B virus X protein, was found to be involved in the development and progression of several tumors. However, the role of URG11 in human non-small cell lung cancer (NSCLC) has not yet been determined. Therefore, the aim of the present study was to explore the role of URG11 in human NSCLC. Our results found that URG11 was highly expressed in human NSCLC tissues compared with matched normal lung tissues, and higher levels were found in NSCLC cell lines in comparison to the normal lung cell line. Moreover, we also found that knockdown of URG11 significantly inhibited proliferation, migration/invasion of NSCLC cells, as well as suppressed tumor growth in vivo. Furthermore, knockdown of URG11 suppressed the expression of β-catenin, c-Myc, and cyclin D1 in NSCLC cells. Taken together, the study reported here provided evidence that URG11 downregulation suppresses proliferation, invasion, and β-catenin expression in NSCLC cells. Thus, URG11 may be a novel potential therapeutic target for NSCLC.
Cite
Citations (6)