Zhongxin Lu

MiR-155 acts as an anti-inflammatory factor in atherosclerosis-Associated foam cell formation by repressing calcium-regulated heat stable protein 1

Atherosclerosis (AS) is chronic inflammation in response to lipid accumulation. MicroRNA-155 (miR-155) is being increasingly studied to evaluate its potential as diagnostic biomarkers and therapeutic targets in many diseases. However, delineating the role of miR-155 in AS remains difficult. Here, we detected constitutive expression of several microRNAs (miRNAs) possibly associated with cardiovascular disease in foam cells and clinical specimens from patients with AS. Among them, we found that the level of miR-155 in foam cells was the most significantly elevated in a dose- and time-dependent manner. In addition, the expression of miR-155 was elevated in the plasma and plaque of patients with AS. We also reported for the first time that miR-155 targets calcium-regulated heat stable protein 1 (CARHSP1), which regulates the stability of tumor necrosis factor alpha (TNF-α) mRNA. Furthermore, we investigated the mechanism by which the miR-155 level is elevated. miR-155 upregulation is due to transcriptional regulation by nuclear factor (NF)-κB, which is activated by the inflammatory factor TNF-α. In summary, increased miR-155 relieves chronic inflammation by a negative feedback loop and plays a protective role during atherosclerosis-associated foam cell formation by signaling through the miR-155–CARHSP1–TNF-α pathway.

Clinical significance and detection of microRNA-21 in serum of patients with diffuse large B-cell lymphoma in Chinese population

Expression patterns of microRNAs in serum are involved in potentially non‐invasive biomarkers for various diseases. The purpose of this study is to examine the expression of miR‐21 in serum of patients with diffuse large B‐cell lymphoma (DLBCL) and to validate the significance of miR‐21 in early diagnosis, genotyping, treatment options as well as its prognosis estimates of Chinese DLBCL.

Huaier suppresses proliferation and induces apoptosis in human pulmonary cancer cells via upregulation of miR-26b-5p.

Various studies have reported that Huaier possesses anti‐tumor effects. However, the mechanisms are not completely elucidated. Here, we found 66 differentially expressed miRNAs in Huaier‐treated pulmonary adenocarcinoma A549 cells, with upregulation of miR‐26b‐5p. Transfection of A549 cells with miR‐26b‐5p mimic inhibited proliferation and induced apoptosis, while transfection of Huaier‐treated A549 cells with a miR‐26b‐5p inhibitor reversed the effects of Huaier. EZH2 was verified as the target of miR‐26b‐5p. Thus, our findings indicate that Huaier might suppress proliferation and induce apoptosis in lung cancer cells via a miR‐26b‐5p‐EZH2‐mediated approach, which provides a new perspective for understanding the anti‐tumor effects of Huaier.

Silencing tankyrase and telomerase promotes A549 human lung adenocarcinoma cell apoptosis and inhibits proliferation

Telomeres are the end structures of chromosomes in mammalian cells; they play a pivotal role in maintaining the stability of the chromosome and become shorter with each cell division. However, several types of tumor cells express telomerase in very high levels to overcome this crisis and achieve the ability to proliferate endlessly. The telomerase inhibitors can partly inhibit tumor cell proliferation and promote apoptosis, but their roles are only limited. Tankyrase is a poly(ADP-ribose) polymerase which has synergistic effect on telomerase, and is expressed in lung cancer cells in high levels. In the present study, antisense oligonucleotides of telomerase (ashTERT) and tankyrase (asTANKS) were used as specific inhibitors to silence the expression of target genes in A549 human lung adenocarcinoma cells by transfection. The results showed that ashTERT and asTANKS suppressed the expression of telomerase and tankyrase significantly; both inhibited the activity of telomerase and the combination group achieved better effect, but only ashTERT shortened the length of telomeres, asTANKS did not. Further studies showed that ashTERT and asTANKS-promoted A549 apoptosis was not mediated by downregulation of the expression of the anti-apoptotic gene BCL-2 or upregulation of the expression of the pro-apoptotic gene BAX, but by adjusting the two isoforms proportion of myeloid cell leukemia-1 (MCL-1) which can interact with tankyrase directly. MCL-1short (MCL-1S), a pro-apoptotic gene, increased more than MCL-1Long (MCL-1L) which is an anti-apoptotic gene, leading to A549 cell apoptosis and a similar result was obtained in nude mice in vivo. The present study suggests that combination of the inhibitors of telomerase and tankyrase can be used as a strategy for the treatment of lung cancer in humans.

Gene expression profiling analysis of hepatocellular carcinoma

BackgroundPrimary hepatocellular carcinoma (HCC) is one of the most common malignancies in the world. However, the molecular pathogenesis of HCC is not well-understood, and the prognosis for patients with HCC remains very poor.MethodsTo disclose detailed genetic mechanisms in hepatocellular carcinoma (HCC) with a view toward development of novel therapeutic targets, we analyzed expression profiles HCCs and their corresponding noncancerous tissues by using bioinformatics method.ResultsIn this paper, we report the identification of genes whose expression has been altered and the changed bio-pathways during hepatocarcinogenesis. Hepatoma cells infect intracellular and intercellular signal transduction through Focal adhesion and cause abnormal expression of important intracellular signaling pathway. In addition, it is worth mentioning that some small molecules still restored to the state similar to normal cells, such as bambuterol and lovastatin. This member gene set would serve as a pool of lead gene targets for the identification and development of novel diagnostic and therapeutic biomarkers to greatly improve the clinical management of HCC patients with different risks of recurrence after curative partial hepatectomy.ConclusionsThe study has great significance for gene therapy and pharmacotherapy and provides a new treatment entry point and a potential new clinical drug for HCC patients.

Demethylation of the MIR145 promoter suppresses migration and invasion in breast cancer

miR-145 has been implicated in the progression of breast cancer. Here, we report that its expression is decreased in breast cancer specimens and cell lines and that this low level of expression is associated with DNA methylation of its gene, MIR145. Methylation of MIR145 has previously been correlated with cell migration and invasion, both in vivo and in vitro. We found that demethylation of MIR145 reactivates miR-145 and contributes to the anti-cancer properties of 5-aza-2′-deoxyazacytidine (5-AzaC). Therefore, miR-145 is a potentially valuable biomarker for breast cancer.

Retraction Note: Gene expression profiling analysis of hepatocellular carcinoma

Primary hepatocellular carcinoma (HCC) is one of the most common malignancies in the world. However, the molecular pathogenesis of HCC is not well-understood, and the prognosis for patients with HCC remains very poor. To disclose detailed genetic mechanisms in hepatocellular carcinoma (HCC) with a view toward development of novel therapeutic targets, we analyzed expression profiles HCCs and their corresponding noncancerous tissues by using bioinformatics method. In this paper, we report the identification of genes whose expression has been altered and the changed bio-pathways during hepatocarcinogenesis. Hepatoma cells infect intracellular and intercellular signal transduction through Focal adhesion and cause abnormal expression of important intracellular signaling pathway. In addition, it is worth mentioning that some small molecules still restored to the state similar to normal cells, such as bambuterol and lovastatin. This member gene set would serve as a pool of lead gene targets for the identification and development of novel diagnostic and therapeutic biomarkers to greatly improve the clinical management of HCC patients with different risks of recurrence after curative partial hepatectomy. The study has great significance for gene therapy and pharmacotherapy and provides a new treatment entry point and a potential new clinical drug for HCC patients.