Zhe Meng

Downregulation of miR-383 promotes glioma cell invasion by targeting insulin-like growth factor 1 receptor.

Invasiveness is a major clinical feature of glioma, an aggressive brain tumor with poor prognosis. Although there is emerging evidence that some microRNAs are involved in the glioma cell invasion process, it remains necessary to find functional microRNAs and elucidate the underlying molecular mechanisms. Here, we reported that a microRNA, miR-383, was downregulated in gliomas and inversely correlated with glioma pathological grades. Downregulation of miR-383 enhanced, whereas upregulation of miR-383 inhibited, the glioma cell invasive ability. Furthermore, we found that downregulation of miR-383 activated the AKT signaling following upregulation of MMP2 expression by directly targeting insulin-like growth factor 1 receptor (IGF1R). Importantly, we demonstrated that IGF1R expression is critical for miR-383 downregulation-induced cell invasion. Taken together, these findings uncover a novel regulatory mechanism for constitutive IGF1R signaling activation in glioma cancer and may provide miR-383 as a useful diagnostic marker or therapeutic target.

Effect of intravenous immunoglobulin treatment on brain interferon-gamma and interleukin-6 levels in a rat kindling model.

Many studies indicate that intravenous immunoglobulin (IgG) therapy may decrease symptoms of epilepsy. In this study, we assessed the effects of intravenous IgG in an experimental rat kindling model and attempted to elucidate the underlying mechanism of the IgG effect. For induction of kindling, Wistar rats received repeated intraperitoneal injections of picrotoxin. The serum level of neuron-specific enolase (NSE) was measured to determine seizure severity. Interferon (IFN)-gamma and interleukin (IL)-6 levels were measured in rat hippocampus homogenates. The serum NSE level and hippocampal IFN-gamma level were significantly higher in fully kindled, untreated rats compared to unkindled control rats, whereas IL-6 levels were similar in all groups. Intravenous IgG-treated kindled rats showed NSE and IFN-gamma levels similar to those of control rats, along with lower seizure severity and longer seizure latent period than fully kindled, untreated rats. These results indicate that intravenous immunoglobulin exerts a protective effect on the neurons of kindled rats, potentially by downregulating cytokines in the brain. These results shed light on the mechanism by which intravenous immunoglobulin decreases the severity of epileptic seizures.

Human intravenous immunoglobulins suppress seizure activities and inhibit the activation of GFAP-positive astrocytes in the hippocampus of picrotoxin-kindled rats.

ABSTRACT We previously showed that human intravenous immunoglobulin (IVIG) can lower seizure severity and prolong seizure latency in picrotoxin-kindled rats. The aim of this study was to further characterize the effects of IVIG on seizure activity and investigate its influence on astrocytes in the hippocampus of picrotoxin-kindled rats. A rat kindling model was established by peritoneal injections of picrotoxin for 21 days in Wistar rats. Seventy-five rats were equally divided into five groups: picrotoxin, IVIG pretreatment, IVIG post-treatment, normal saline control, and IVIG control. Seizure severity was evaluated according to a six-stage classification. The number and morphology of glial fibrillary acidic protein (GFAP)-positive astrocytes were studied by immunohistochemistry using the anti-GFAP antibody. The cross-sectional area and grayscale of GFAP-positive astrocytes were also determined. In picrotoxin-kindled rats, pretreatment with IVIG appeared to inhibit full kindling rates, and it significantly reduced the number of GFAP-positive cells in the hippocampus (p < .001). IVIG also significantly (p < .001) attenuated the increase in the cross-sectional area and grayscale of GFAP-positive astrocytes in the hippocampus. Our results suggest that by suppressing the expression of GFAP, IVIGs may reduce seizure activity and inhibit the activation of GFAP-positive astrocytes in picrotoxin-kindled rats.

Knockdown of long non‑coding RNA HOTAIR sensitizes hepatocellular carcinoma cell to cisplatin by suppressing the STAT3/ABCB1 signaling pathway

Long non-coding RNA HOX transcript antisense RNA (HOTAIR) has been demonstrated to exhibit oncogenic activity in several types of cancer, including hepatocellular carcinoma (HCC). However, the association between HOTAIR and HCC multidrug resistance remains uncertain. The present study aimed to investigate the role of HOTAIR in HCC chemoresistance; it was found that knockdown of HOTAIR expression in HCC Huh7 cells resulted in decreased cell proliferation and increased chemosensitivity to cisplatin. Furthermore, expression levels of ATP binding cassette subfamily B member 1 (ABCB1) mRNA and protein were decreased in Huh7 cells upon HOTAIR-knockdown. In addition, HOTAIR-knockdown reduced the levels of phosphorylated signal transducer and activator of transcription 3 (STAT3), and inhibition of STAT3 phosphorylation reduced HOTAIR-mediated ABCB1 expression. Together, these findings indicated that knockdown of HOTAIR in Huh7 cells decreased STAT3 activity and ABCB1 expression, and increased chemosensitivity to cisplatin. Thus HOTAIR could serve as a novel potential therapeutic target to reverse multidrug resistance in HCC.

A rare de novo interstitial duplication of 15q15.3q21.2 in a boy with severe short stature, hypogonadism, global developmental delay and intellectual disability

BackgroundInterstitial duplications distal to 15q13 are very rare.Case PresentationHere, we reported a 14-year-old boy with severe short stature, delayed bone age, hypogonadism, global developmental delay and intellectual disability. His had distinctive facial features including macrocephaly, broad forehead, deep-set and widely spaced eyes, broad nose bridge, shallow philtrum and thick lips. A de novo 6.4 Mb interstitial duplication of 15q15.3q21.2 was detected by chromosomal microarray analysis. We compared our patient’s clinical phenotypes with those of several individuals with overlapping duplications and several candidate genes responsible for the phenotypes were identified as well.ConclusionThe results suggest a novel contiguous gene duplication syndrome characterized with shared features including short stature, hypogonadism, global developmental delay and other congenital anomalies.

Hepatitis C virus core protein regulates OCT4 expression and promotes cell cycle progression in hepatocellular carcinoma

Hepatitis C virus (HCV) core protein plays an important role in the development of hepatocellular carcinoma. octamer-binding protein 4 (OCT4) is critically essential for the pluripotency and self-renewal of embryonic stem cells. Abnormal expression of OCT4 has been detected in several human solid tumors. However, the relationship between HCV core and OCT4 remains uncertain. In the present study, we found that HCV core is capable of upregulating OCT4 expression. The effect of HCV core-induced OCT4 overexpression was abolished by RNAi-mediated scilencing of HCV core. In addition, HCV core-induced OCT4 overexpression resulted in enhanced cell proliferation and cell cycle progression. Inhibition of OCT4 reduced the CCND1 expression and induced G0/G1 cell cycle arrest. Furthermore, OCT4 protein directly binds to CCND1 promoter and transactivates CCND1. These findings suggest that HCV core protein regulates OCT4 expression and promotes cell cycle progression in hepatocellular carcinoma providing new insight into the mechanism of hepatocarcinogenesis by HCV infection.

Hepatitis C virus core protein increases Snail expression and induces epithelial-mesenchymal transition through the signal transducer and activator of transcription 3 pathway in hepatoma cells: HCV core regulates Snail and EMT in HCC

Aberrant expression of Snail, a mediator of epithelial–mesenchymal transition (EMT), is crucial for cancer invasiveness and metastasis. Although hepatitis C virus (HCV) core protein has been implicated in hepatocarcinogenesis, the relationship between HCV core and Snail expression has not been clarified.

Hepatitis C virus core protein increases Snail expression and induces epithelial–mesenchymal transition through the signal transducer and activator of transcription 3 pathway in hepatoma cells

Aberrant expression of Snail, a mediator of epithelial–mesenchymal transition (EMT), is crucial for cancer invasiveness and metastasis. Although hepatitis C virus (HCV) core protein has been implicated in hepatocarcinogenesis, the relationship between HCV core and Snail expression has not been clarified.

LncRNA HOTAIR epigenetically suppresses miR-122 expression in hepatocellular carcinoma via DNA methylation

Background MicroRNA-122 (miR-122), a pivotal liver-specific miRNA, is frequently repressed in hepatocellular carcinoma (HCC) and associated with poor prognosis. Long non-coding RNA (lncRNA) HOTAIR has been proved to function as an oncogene in multiple cancers including HCC. However, the relationship between HOTAIR and miR-122 in HCC remains largely unknown. Methods We investigated the function of HOTAIR and miR-122 in HCC cell models and a xenograft mouse model. The regulatory network between HOTAIR and miR-122 was further detected following overexpression or knockdown of HOTAIR. DNA methylation status of miR-122 promoter region, as well as expression levels of DNMTs, EZH2 and Cyclin G1 were analyzed. Findings In this study, we found that HOTAIR was highly expressed whereas miR-122 was suppressed in HCC, and HOTAIR negatively regulated miR-122 expression in HCC cells. Furthermore, knockdown of HOTAIR dramatically inhibited HCC cell proliferation and induced cell cycle arrest in vitro and suppressed tumorigenicity in vivo by upregulating miR-122 expression. Mechanistically, a CpG island was located in the miR-122 promoter region. HOTAIR epigenetically suppressed miR-122 expression via DNMTs-mediated DNA methylation. Moreover, HOTAIR upregulated DNMTs expression via EZH2. In addition, suppression of miR-122 induced by HOTAIR directly reactivated oncogene Cyclin G1 expression. Collectively, our results suggest that HOTAIR epigenetically suppresses miR-122 expression via DNA methylation, leading to activation of Cyclin G1 and promotion of tumorigenicity in HCC, which provide new insight into the mechanism of HOTAIR-mediated hepatocarcinogenesis via suppressing miR-122.

Hepatitis C virus core protein increases Snail expression and induces Epithelial‐Mesenchymal Transition via STAT3 pathway in hepatoma cells

Aberrant expression of Snail, a mediator of epithelial–mesenchymal transition (EMT), is crucial for cancer invasiveness and metastasis. Although hepatitis C virus (HCV) core protein has been implicated in hepatocarcinogenesis, the relationship between HCV core and Snail expression has not been clarified.