<p>B3GNT3, a Direct Target of miR-149-5p, Promotes Lung Cancer Development and Indicates Poor Prognosis of Lung Cancer</p>
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B3GNT3 (β1, 3-N-acetylglucosaminyltransferase-3) belongs to the β3GlcNAcT family and is essential to form extended core 1 oligosaccharides. Previous studies revealed that B3GNT3 expression was dysregulated in multiple cancers. Here, we aimed to understand the expression profile and function of B3GNT3 in lung cancer.The expression of B3GNT3 was measured by immunohistochemistry and public database analysis. B3GNT3 was knocked down to evaluate the lung cancer cell proliferation, migration and invasion in in vitro and in vivo tumor formation experiments. miR-149-5p targeting B3GNT3 was identified with TargetScan analysis and confirmed with reporter assay. Overexpression of miR-149-5p was achieved using microRNA mimics and function of microRNA-149-5p/B3GNT3 axis was tested in vitro.B3GNT3 was upregulated in lung cancer, and B3GNT3 overexpression was associated with poor prognosis of lung cancer patients. High expression of B3GNT3 was associated with advanced TNM stages, larger tumor size, tumor metastasis and recurrence. Functionally, we demonstrated that knockdown of B3GNT3 suppressed lung cancer cell growth and invasion in vitro. Knockdown of B3GNT3 suppressed lung cancer development in a xenograft tumor model. Moreover, miR-149-5p was validated to negatively regulate B3GNT3 expression through directly targeting B3GNT3 3'-UTR. Overexpression of miR-149-5p could antagonize the tumorigenesis effect of B3GNT3 in vitro.In summary, our study demonstrated that B3GNT3 overexpression was correlated with poor prognosis of lung cancer patient, indicating that B3GNT3 could be a promising prognostic biomarker for lung cancer. miR-149-5p negatively regulated B3GNT3 expression, which might be utilized for therapeutic target in lung cancer.Background: Long noncoding RNA SNHG10 has been reported to promote the development of liver cancer. While by analyzing The Cancer Genome Atlas (TCGA) dataset we observed the downregulation of SNHG10 in non-small cell lung cancer (NSCLC). This study aimed to investigate the roles of SNHG10 in NSCLC. Materials and Methods: This study included 60 pairs of NSCLC and nontumor tissue samples collected from 60 NSCLC patients (males and females, 39–66 years, 50.9 ± 5.5 years). Gene expression was detected by quantitative polymerase chain reaction and western blot. Overexpression experiments were used to analyze gene interactions. Effects of cell transfections on cell proliferation were analyzed by performing CCK-8 cell proliferation assays. Results: We confirmed the downregulation of SNHG10 in NSCLC. In addition, low expression level of SNHG10 predicted the poor survival of NSCLC patients. SNHG10 can directly interact with miR-543, while overexpression of miR-543 failed to downregulate SNHG10. However, SNHG10 overexpression led to upregulation of sirtuin 1 (SIRT1), a downstream target of miR-543. Cell proliferation assay showed that SNHG10 and SIRT1 overexpression led to the decreased proliferation rate of NSCLC cells. In contrast, miR-543 over-expression played an opposite role and reduced the effects of SNHG10 and SIRT1 overexpression. Conclusions: In conclusion, SNHG10 sponges miR-543 to upregulate tumor suppressive SIRT1 in NSCLC to suppress cell proliferation.
Sirtuin 1
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MicroRNA (miRNA) is an important type of non-coding RNAs with both physiological and pathological functions in human beings. Aberrant expression of miRNAs has been found in tumor tissues and the expression profile of certain groups of miRNAs is now emerging as bio-marker for cancer. It has been confirmed that miRNAs can exert oncogenic or tumor-suppressive functions through repressing the expression of their target genes which play different roles in tumorigenesis. The identification of oncogenic or tumor-suppressive miRNAs allows potential applications of these miRNAs as targets for cancer chemotherapy. In this review, we summarized the well-known cancer-related miRNAs reported in recent years and the roles they played in tumorigenesis and progression by targeting specific genes. Strategies developed to modulate the function or expression of the dysregulated miRNAs are also reviewed with recent examples illustrating their potential applications in cancer chemotherapy. Keywords: MicroRNA, oncogenic, tumor-suppressive, up-regulation, down-regulation, tumorigenesis, cancer chemotherapy.
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MicroRNA (miRNA ) 是在长度的 2123 核苷酸的小非编码的 RNA 分子的簇，它在 post-transcriptional 水平控制目标基因的表达式。最近的研究显示了 miRNA 在 carcinogenesis 起一个必要作用，例如影响房间生长，区别， apoptosis，和房间周期。现在，涉及 carcinogenesis 的 miRNA 的多重答应角色正在出现，并且 miRNA 仔细联系到 epithelialmesenchymal 转变(EMT ) 的进程，这被显示出，癌症干细胞(CSC ) 的规定，肿瘤侵略和移植的开发。miRNA 也充当稳定地在浆液表示的 biomarker 并且为各种各样的癌症的分子的目标治疗提供新目标。这评论的目的是在 carcinogenesis 说明 miRNA 的新角色并且在癌症加亮 miRNA 的新前景临床的申请，例如在血清学的诊断和分子目标的治疗学。
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Overexpression of members of the HER/erbB transmembrane tyrosine kinase family like HER2/erbB2/neu is associated with various cancers. Some heterodimers, especially HER2/HER3 heterodimers, are particularly potent inducers of oncogenic signaling. Still, from a clinical viewpoint their inhibition has yielded only moderate success so far, despite promising data from cell cultures. This suggests acquired resistance upon inhibitor therapy as one putative issue, requiring further studies in cell culture also aiming at rational combination therapies. In this paper, we demonstrate in ovarian carcinoma cells that the RNAi-mediated single knockdown of HER2 or HER3 leads to the rapid counter-upregulation of the respective other HER family member, thus providing a rational basis for combinatorial inhibition. Concomitantly, combined knockdown of HER2/HER3 exerts stronger anti-tumor effects as compared to single inhibition. In a tumor cell line xenograft mouse model, therapeutic intervention with nanoscale complexes based on polyethylenimine (PEI) for siRNA delivery, again reveals HER3 upregulation upon HER2 single knockdown and a therapeutic benefit from combination therapy. On the mechanistic side, we demonstrate that HER2 knockdown or inhibition reduces miR-143 levels with subsequent de-repression of HER3 expression, and validates HER3 as a direct target of miR-143. HER3 knockdown or inhibition, in turn, increases HER2 expression through the upregulation of the transcriptional regulator SATB1. These counter-upregulation processes of HER family members are thus based on distinct molecular mechanisms and may provide the basis for the rational combination of inhibitors.
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The balance between Ang II/AT1R and Ang-(1-7)/Mas plays a pivotal role in the development of lipopolysaccharides (LPS)-induced acute respiratory distress syndrome. However, the mechanisms underlying the balancing process still remain unclear. Here we investigated the roles of nuclear factor (NF)-κB and p53 in regulating AT1R and Mas expression. The results demonstrated that Ang II pretreatment resulted in downregulation of Mas and upregulation of AT1R, phosphorylated p65, and apoptosis in LPS-treated Human pulmonary microvascular endothelial cells (HPMVECs), but had no effect on p53 expression. Lentiviral vector-mediated P65 knockdown, but not a P53 knockdown, reversed all these effects of Ang II. On the other hand, Ang-(1-7) pretreatment lead to an increased in Mas expression and a decrease in AT1R, p53, and phosphorylated p65 expressions with suppressed apoptosis in LPS-treated cells. P65 knockdown promoted the protein expression of both AT1R and Mas while inhibiting p53 expression. P53 knockdown, but not a p65 knockdown, reversed all these effects of Ang-(1-7). Interestingly, p65 overexpression upregulated p53 and AT1R but downregulated Mas. P53 knockdown activated p65. These results suggest that there is a two-way feedback regulation between AT1R and Mas receptor via the NF-kB p65/P53 pathway, which may play a key role in LPS-induced HPMVECs apoptosis.
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Abstract Approximately 25,000 ovarian cancers are diagnosed in the United States annually, and 75% of cases are in the advanced stage when they are largely incurable. There is a critical need for improved early detection tools and development of novel treatments. Recently, we showed that among 20q13‐amplified genes in ovarian cancer, ADRM1 overexpression was the most highly correlated with amplification and was significantly upregulated with respect to stage, recurrence, and metastasis. In addition, overexpression of ADRM1 correlated significantly with shorter time to recurrence and overall survival. Herein, array‐CGH and microarray expression of ovarian cancer cell lines provides evidence consistent with the primary tumor data that ADRM1 is a 20q13 amplification target. Knockdown of ADRM1 in amplified ovarian cell‐line OAW42 results in downregulation of growth factor GIPC1 and upregulation of tumor‐suppressor RECK RNA and protein. In our dataset of 141 ovarian primary tumors, ADRM1 overexpression significantly correlates with GIPC1 overexpression. In addition, there is a significant anticorrelation between ADRM1 overexpression and RECK expression. Further research is necessary to determine whether targeting knockdown of ADRM1 in 20q13‐amplified ovarian cancers results in growth inhibition and tumor suppression via downstream targets GIPC1 and RECK . © 2011 Wiley‐Liss, Inc.
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Abstract A new class of regulatory molecules known as microRNAs (miRNAs) is redefining our understanding of the molecular pathways associated with tumorigenesis. These miRNAs are small noncoding RNA (ncRNA) sequences with potent regulatory potential. The aberrant expression of miRNAs has been associated with the development of various tumors. It has been suggested that miRNAs can both regulate and act as tumor‐suppressor genes and oncogenes. Our understanding of the role of miRNAs in head and neck tumorigenesis is in its infancy. However, several recent studies have revealed extensive dysregulation of miRNA in head and neck tumors and have highlighted the potential of certain miRNAs to act as diagnostic and prognostic markers and targets for new therapeutic agents. The intent of this review is to discuss and summarize current findings that point to a significant role for miRNAs in head and neck tumorigenesis. © 2010 Wiley Periodicals, Inc. Head Neck, 2010
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SNGH5 and TGFBR3 messenger RNA were downregulated while miR-181a-5p was upregulated in osteoarthritis tissues and models. Knockdown of SNGH5 impeded chondrocytes proliferation, while accelerated the apoptosis. However, miR-181a-5p had opposite effects. TGFBR3 was identified as a target gene of miR-181a-5p, which could be indirectly suppressed by SNGH5 knockdown. Taken together, downregulation of SNGH5 could inhibit the proliferation abilities of chondrocytes and facilitate apoptosis via regulating the miR-181a-5p/TGFBR3 axis
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