CA : A Cancer Journal for Clinicians

MicroRNAs (miRNAs) are endogenous ∼23 nt RNAs that play important gene-regulatory roles in animals and plants by pairing to the mRNAs of protein-coding genes to direct their posttranscriptional repression. This review outlines the current understanding of miRNA target recognition in animals and discusses the widespread impact of miRNAs on both the expression and evolution of protein-coding genes.

MicroRNAs: Target Recognition and Regulatory Functions

MicroRNAs (miRNAs) are a group of noncoding RNA molecules of 20-23 nucleotides length that negatively regulate gene expressions in numerous cellular processes. Through complementary paring with target mRNAs, miRNAs have frequently emerged as dual regulators of cancer development by acting on multiple signaling pathways, thereby act as novel biomarkers for cancer diagnosis, prognosis, and prediction of response to treatment. As one of them, miR-30a has been found to act as an onco-suppressor of tumorigenesis pathways through inhibition of cellular proliferation, migration and invasion. Simultaneously, miR-30a plays a progressing role in several types of cancer, determined by relevant target genes as well. In the present review, we summarize recent research regarding miR-30a, including its biological function, expression and regulation, especially focusing on its role in cancer development and progression. Clinically, miR-30a may serve as a potential target in the diagnosis and therapy of human cancer.

/pdf/the-versatile-role-of-microrna-30a-in-human-cancer-l2fulfkxas.pdf

The Versatile Role of microRNA-30a in Human Cancer

Nickel is associated with reproductive toxicity. However, the reproductive toxicity of nickel nanoparticles (Ni NPs) is unclear. Our goal was to determine the association between nickel nanoparticle exposure and reproductive toxicity. According to the one-generation reproductive toxicity standard, rats were exposed to nickel nanoparticles by gavage and we selected indicators including sex hormone levels, sperm motility, histopathology, and reproductive outcome etc. Experimental results showed nickel nanoparticles increased follicle stimulating hormone (FSH) and luteinizing hormone (LH), and lowered etradiol (E2) serum levels at a dose of 15 and 45 mg/kg in female rats. Ovarian lymphocytosis, vascular dilatation and congestion, inflammatory cell infiltration, and increase in apoptotic cells were found in ovary tissues in exposure groups. For male rats, the weights decreased gradually, the ratio of epididymis weight over body weight increased, the motility of rat sperm changed, and the levels of FSH and testosterone (T) diminished. Pathological results showed the shedding of epithelial cells of raw seminiferous tubule, disordered arrangement of cells in the tube, and the appearance of cell apoptosis and death in the exposure group. At the same time, Ni NPs resulted in a change of the reproductive index and the offspring development of rats. Further research is needed to elucidate exposure to human populations and mechanism of actions.

Nickel Nanoparticles Exposure and Reproductive Toxicity in Healthy Adult Rats

Environmental mixtures of nanomaterials and chemicals: The Trojan-horse phenomenon and its relevance for ecotoxicity.

This study was carried out to add scientific data in regard to the use of metallic nanoparticles in nanomedicine. The acute toxicity of nickel (Ni) nanoparticles (50 nm), intravenously injected through the dorsal penile vein of Sprague Dawley rats was evaluated in this study. Fourteen days after injection, Ni nanoparticles induced liver and spleen injury, lung inflammation, and caused cardiac toxicity. These results indicate that precautionary measures should be taken with regard to the use of Ni nanoparticles or Ni compounds in nanomedicine.

/pdf/acute-toxicity-of-nickel-nanoparticles-in-rats-after-4xys7phohw.pdf

Acute toxicity of nickel nanoparticles in rats after intravenous injection.

Due to their chemical stability and nonallergic, nonirritant, and ultraviolet protective properties, titanium dioxide (TiO2) nanoparticles (NPs) have been widely used in industries such as electronics, optics, and material sciences, as well as architecture, medicine, and pharmacology. However, increasing concerns have been raised in regards to its ecotoxicity and toxicity on the aquatic environment as well as to humans. Although insights have been gained into the effects of TiO2 NPs on susceptible biological systems, there is still much ground to be covered, particularly in respect of our knowledge of the effects of the interaction of TiO2 NPs with other chemicals or physical factors. Studies suggest that interactions of TiO2 NPs with other chemicals or physical factors may result in an increase in toxicity or adverse effects. This review highlights recent progress in the study of the interactive effects of TiO2 NPs with other chemicals or physical factors.

https://www.dovepress.com/getfile.php?fileID=16767

Toxic effects of the interaction of titanium dioxide nanoparticles with chemicals or physical factors

The expression and clinical significance of insulin-like growth factor 1 (IGF-1), insulin-like growth factor binding protein 3 (IGFBP-3), and insulin-like growth factor binding protein 7 (IGFBP-7) were investigated in serum and lung cancer tissues from 57 patients with non-small cell lung cancer (NSCLC). Lung cancer tissues at different pathologic stages (27 patients at stages I-II and 30 patients at stages III-IV), normal lung tissues from 17 patients with benign pulmonary disease, and serum samples from both lung cancer and benign pulmonary disease patients were collected during surgery. Enzyme-linked immunosorbent assay and avidin-biotin-peroxidase complex immunohistochemical staining were used to detect IGF-1, IGFBP-3, and IGFBP-7 expression in serum and tissues, respectively. The results show that expression of IGF-1 in lung cancer tissues and serum from NSCLC patients were significantly higher than in the control (P < 0.05). However, expression of IGFBP-3 and IGFBP-7 in cancer tissues and serum from NSCLC patients was significantly lower than in the control (P < 0.05). These results suggest that upregulation of IGF-1 and downregulation of IGFBP-3 and IGFBP-7 may be potential diagnostic biomarkers for NSCLC.

/pdf/expression-and-clinical-significance-of-igf-1-igfbp-3-and-10gbeoq4rr.pdf

Expression and clinical significance of IGF-1, IGFBP-3, and IGFBP-7 in serum and lung cancer tissues from patients with non-small cell lung cancer

To investigate the inhibitory effects of microRNA-30d (miR-30d) on renal carcinoma cell proliferation and the underlying molecular mechanisms, miR-30d expression in renal cell carcinoma (RCC) specimens was analyzed by quantitative polymerase chain reaction (qPCR). The inhibition of the proliferation of miR-30d on renal carcinoma cells (ACHN cell line) was analyzed by MTT and colony formation assays. The effects of miR-30d on cyclin E2 expression were detected by the luciferase activity of the reporter gene. In addition, the effects of miR-30d on endogenous cyclin E2 expression at the RNA and protein levels were investigated by qPCR and western blot analysis, respectively. Cell cycles were analyzed by flow cytometry. The results showed the following: i) Expression of miR-30d was significantly downregulated in renal carcinoma tissues compared with paraneoplastic tissues; ii) overexpression of miR-30d inhibited renal carcinoma cell proliferation and colony formation; iii) miR-30d inhibited cyclin E2 3′ untranslated region-mediated reporter gene expression; and iv) overexpression of miR-30d downregulated endogenous cyclin E2 expression and blocked the cell cycle at the G1 phase. In conclusion, miR-30d functions as a tumor suppressor gene in RCC and inhibits renal carcinoma cell proliferation. Cell cycle regulatory factor cyclin E2 is a target gene of miR-30d. miR-30d inhibits renal carcinoma cell proliferation via the regulation of cyclin E2 expression at the post-transcriptional level.

/pdf/proliferation-inhibition-and-the-underlying-molecular-5581npeuac.pdf

Proliferation inhibition and the underlying molecular mechanisms of microRNA-30d in renal carcinoma cells.

Background 
The genetic polymorphisms of glutathione S-transferase (GSTs) have been suspected to be related to the development of lung cancer while the current results are conflicting, especially in the Chinese population.
Methods 
Data on genetic polymorphisms of glutathione S-transferase Mu 1 (GSTM1) from 68 studies, glutathione S-transferase theta 1 (GSTT1) from 17 studies and GSTM1-GSTT1 from 8 studies in the Chinese population were reanalyzed on their association with lung cancer risk. Odds ratios (OR) were pooled using forest plots. 9 subgroups were all or partly performed in the subgroup analyses. The Galbraith plot was used to identify the heterogeneous records. Potential publication biases were detected by Begg's and Egger's tests.
Results 
71 eligible studies were identified after screening of 1608 articles. The increased association between two vital GSTs genetic polymorphisms and lung cancer risk was detected by random-effects model based on a comparable heterogeneity. Subgroup analysis showed a significant relationship between squamous carcinoma (SC), adenocarcinoma (AC) or small cell lung carcinoma (SCLC) and GSTM1 null genotype, as well as SC or AC and GSTT1 null genotype. Additionally, smokers with GSTM1 null genotype had a higher lung cancer risk than non-smokers. Our cumulative meta-analysis demonstrated a stable and reliable result of the relationship between GSTM1 null genotype and lung cancer risk. After the possible heterogeneous articles were omitted, the adjusted risk of GSTs and lung cancer susceptibility increased (fixed-effects model: ORGSTM1 = 1.23, 95% CI: 1.19 to 1.27, P<0.001; ORGSTT1 = 1.18, 95% CI: 1.10 to 1.26, P<0.001; ORGSTM1-GSTT1 = 1.33, 95% CI: 1.10 to 1.61, P = 0.004).
Conclusions 
An increased risk of lung cancer with GSTM1 and GSTT1 null genotype, especially with dual null genotype, was found in the Chinese population. In addition, special histopathological classification of lung cancers and a wide range of gene-environment and gene-gene interaction analysis should be taken into consideration in future studies.

/pdf/the-associations-between-two-vital-gsts-genetic-3pvsij6fx8.pdf

Xialu Lin

Papers

Acute toxicity of nickel nanoparticles in rats after intravenous injection.

Toxic effects of the interaction of titanium dioxide nanoparticles with chemicals or physical factors

Expression and clinical significance of IGF-1, IGFBP-3, and IGFBP-7 in serum and lung cancer tissues from patients with non-small cell lung cancer

Proliferation inhibition and the underlying molecular mechanisms of microRNA-30d in renal carcinoma cells.

The Associations between Two Vital GSTs Genetic Polymorphisms and Lung Cancer Risk in the Chinese Population: Evidence from 71 Studies