The discovery of large numbers of long non-coding RNAs (lncRNAs) has been driven by genome-wide transcriptional analyses. Compared to small ncRNAs, lncRNAs have been shown to harbor biological activities, but the functions of the great majority of lncRNAs are not known. There is growing evidence that lncRNAs can regulate gene expression at epigenetic, transcription, and post-transcription levels and widely take part in various physiological and pathological processes, such as participating in cell development, immunity, oncogenesis, clinical disease processes, etc. Here, the current research efforts on the function of lncRNA in recent years were summarized.

MicroRNAs (miRNAs) are a class of 18-27-nucleotides single-stranded RNA molecules that regulate gene expression at the post-transcriptional level. It has been demonstrated that miRNAs regulate a variety of physiological functions, including development, cell differentiation, proliferation, and apoptosis. There are growing evidence showed that miRNAs can affect the genesis and development of tumor and play a kind of tumor suppressor or oncogenic function by regulating its targetted gene-related signal pathway. miRNA-21 is one of the early discovered miRNAs in human cells, and the expression of miRNA-21 is significantly upregulated in different kinds of solid tumors. Its abnormal expression levels are closely associated with pathogenesis of cancers. This review summarizes the recent study on the field of miRNA-21 and its association with cancer.

Recently, using large-scale genomic sequencing, a great number of small noncoding RNAs (ncRNA) has been discovered. Short ncRNAs can be classified into three major classes--small interfering RNA (siRNA), microRNA (miRNA), and piwi-interacting RNA (piRNA). These short ncRNAs ranging from 20 to 300 nt in size are now recognized as a new paradigm of gene regulation for controlling many biological processes. In this paper, we review the biogenesis and recent research on the functions of small regulatory non-coding RNAs and aim at understanding their important functions in living organisms.

Glioblastoma multiforme (GBM) is an incurable malignant brain tumor, usually fatal within 1 year of diagnosis. Using a syngeneic rat 9L gliosarcoma model, we have developed a novel drug delivery method in which naked plasmid DNA is selectively targeted to brain tumors via intra-arterial injection. Using a plasmid encoding the antiangiogenic endostatin, transgene expression can be detected in tumor cells in vivo, and therapeutic efficacy is observed. Administration of this plasmid resulted in an 80% tumor volume reduction 1 week after treatment and enhanced survival time by up to 47%.Treated tumors exhibited a 40% decrease in the number of tumor vessels; ultrastructural analysis of remaining tumor vessels demonstrated a number of changes including markedly narrowed or collapsed lumens. We conclude that intra-arterial injection of plasmids selectively targets therapeutic genes to CNS neoplasms. This method of gene therapy holds promise for the treatment of these highly malignant brain tumors.

Hollow mesoporous silica nanospheres functionalized with aggregation-induced emission (AIE) luminogen tetraphenylethene were prepared by postgrafting method. The as-prepared inorganic-organic hybrid nanospheres show bright blue emission and good biocompatibility as shown by MTT assays. The large cavities of the materials enable high loading of the anticancer drug doxorubicin hydrochloride (DOX), and the mesoporous silica shells allow pH-dependent drug release. The materials can be effectively taken up by cells and function as luminescent bioprobes, demonstrating their potential application in imaging-guided therapy.

Liver cancer is the second leading cause of cancer death. Due to treatments failures from drug resistance and cancer metastasis, discovering more effective treatments is imperative. As an angiogenesis inhibitor extracted from the Chinese herb-Safflower, hydroxysafflor yellow A (HSYA) inhibits the tumor growth in H22-bearing mice. Poorly differentiated hepatoma cells showed the ability to invade and metastasize, which are dependent on the angiogenesis. Accordingly, we hypothesized that HSYA could inhibit the metastasis of liver cancer cells. We investigated the metastasizing potential of human hepatic carcinoma SMMC-7721 cells treated with HSYA. A pulmonary metastatic model of mouse hepatoma H22 cells was established to evaluate the effect and possible mechanism of HSYA on lung metastasis from liver cancer. The results showed that HSYA inhibited the proliferation, invasion and migration of SMMC-7721 cells and reduced its adhesion to the extracellular matrix (ECM). In H22 mice treated with HSYA, the formation of E-cadherin/β-catenin complex resulted in the activation of peroxisome proliferator-activated receptor γ and inhibition of matrix metalloproteinase-2. As a result, the degradation of ECM was reduced and epithelial-mesenchymal transition was prevented. The present findings indicate that HSYA can prevent pulmonary metastasis in liver cancer, which provides strong evidence for the application of HSYA in treatments.

BackgroundAnti-tumor properties of hydroxysafflor-yellow A (HSYA) have been recently revealed, as a series of apoptotic factors were confirmed to be regulated by HSYA and associated with peroxisome proliferator-activated receptor Gamma (PPARγ). In this study, we investigated the cell apoptosis mechanism of HSYA via activated PPARγ signal in human gastric carcinoma cells.Material/MethodsBGC-823 cells were cultured and divided into 5 independent groups: Tumor, HSYA, HSYA+PPARγ inhibitor (GW9662), and PPARγ agonist (RGZ), RGZ+GW9662. Cell proliferative activity was measured by MTT. Apoptosis and cell cycle were detected by flow cytometry. The nuclear translocation of PPARγ was detected by immunofluorescence staining chemistry, and mRNA levels of PPARγ and caspase-3 were measured by real-time qPCR.ResultsCompared to the RGZ group, the HSYA group (100 μM) showed a similar inhibitory effect on the proliferation process of BGC-823 cells, inducing their apoptosis. As a result, the transition of BGC-823 cells from G0/G1 phase to S phase was blocked. HSYA was also found to promote the nuclear translocation of PPARγ, leading to increased expression of PPARγ and caspase-3. The regulatory effect of HSYA on BGC-823 cells could be further inhibited by PPARγ inhibitor in group GW9662.ConclusionsWe report the inhibitory effect of HSYA on the proliferation of BGC-823 cells, which results in activating PPARγ-dependent cell cycle blocking and cell apoptosis, suggesting that PPARγ is a specific type of HSYA that can induce apoptosis of BGC-823 cells.

Increasing evidence suggests that the alteration of global histone H4K16 acetylation (H4K16ac) may be involved in several types of cancer. It is known that the global histone H4K16ac level in cells is controlled by several enzymes including histone acetyltransferases (HATs) and histone deacetylases (HDACs). We report in detail which particular enzyme is responsible for global reduction of histone H4K16ac in gastric cancer. Our study included 156 frozen tissue samples of primary diagnosed gastric cancer tissues and matched adjacent or normal tissues, and the gastric cancer cells SGC-7901 and MGC-803. The reverse transcription polymerase chain reaction (RT-PCR), western blot, transient transfection and siRNA knockdown approaches were used. Statistical analysis of the qRT-PCR data revealed that a significant reduction (>2-fold decreased) of hMOF expression in gastric cancer tissues in 81% (42/52) of patients. In patients with gastric cancer, downregulation of hMOF was connected to gastric cancer and tissues with pT2-T4 tumor status, lymph node metastasis and distant metastasis. Overall survival rates revealed a significant difference between the low- and high-hMOF expression groups. However, there was no significant difference by age, gender and cell differentiation. In SGC-7901 and MGC-803 gastric cancer cells, as expected, low expression of hMOF and decreased global histone H4K16ac were observed. Although we did not obtained a statistically significant high-level of HDAC4 in tumor tissues, increased HDAC4 in both gastric cancer cell lines was detected. Therefore, overexpression of hMOF and knockdown of HDAC4 experiments were carried out to investigate the potential coordinating role between hMOF and HDAC4 on global histone H4K16ac in gastric cancer. Overexpression of hMOF increased global H4K16ac in cells, however, no obvious increase of global H4K16ac in HDAC4 knockdown MGC-803 cells was observed. Histone acetyltransferase hMOF and global histone H4K16ac status might be involved in gastric cancer tumorigenic pathways. hMOF, but not HDAC4, is mainly responsible for global histone H4K16ac acetylation in gastric cancer cells.