MicroRNAs (miRNAs) may function as oncogenes or tumor-suppressor genes depending on the targets that are regulated. Enhancer of zeste homolog 2 (EZH2) is the target of miR-101 and a member of the polycomb repressive complex 2, which is involved in the methylation of histone H3 at lysine 27 (H3K27). Therefore, we aimed to ascertain whether or not the overexpression of miR-101 inhibits invasion of lung cancer through regulation of EZH2. In this study, the expression of miR-101 was down-regulated and the expression of EZH2 was up-regulated in lung cancer. Global methylation of H3K27 was higher in metastatic lung cancer than in early lung cancer lesions. Overexpression of miR-101 induced a marked reduction in EZH2 mRNA levels in several lung cancer cell lines. A reduction in the trimethyl H3K27 histone mark was detected at the CDH1 promoter in miR-101 precursor-transfected cells. Moreover, the expression of CDH1 and MMP-2 was reversed by miR-101 transfection. Therefore, the overexpression of miR-101 inhibits the invasiveness of lung cancer. miR-101 may be a potent tumor suppressor by altering chromatin structure through repression of EZH2 and may be a potential therapeutic tool for patients with lung cancer.

During the outbreak of the Middle East Respiratory Syndrome (MERS) in Korea in 2015, the Korea Centers for Disease Control and Prevention (KCDC) confirmed a case of MERS in a healthcare worker in Daejeon, South Korea. To verify the precise route of infection for the case, we conducted an in-depth epidemiological investigation in cooperation with the KCDC. We reviewed the MERS outbreak investigation report of the KCDC, and interviewed the healthcare worker who had recovered from MERS. Using the media interview data, we reaffirmed and supplemented the nature of the exposure. The healthcare worker, a nurse, was infected while performing cardiopulmonary resuscitation (CPR) for a MERS patient in an isolation room. During the CPR which lasted for an hour, a large amount of body fluid was splashed. The nurse was presumed to have touched the mask to adjust its position during the CPR. She suggested that she was contaminated with the MERS patient's body fluids by wiping away the sweat from her face during the CPR. The possible routes of infection may include the following: respiratory invasion of aerosols contaminated with MERS-coronavirus (MERS-CoV) through a gap between the face and mask; mucosal exposure to sweat contaminated with MERS-CoV; and contamination during doffing of personal protective equipment. The MERS guidelines should reflect this case to decrease the risk of infection during CPR.

MicroRNAs (miRNAs) play a significant role in cancer development and progression by regulating the expression of proto-oncogenes or tumor suppressor genes. Our previous study using microarrays demonstrated that miR-99b was downregulated in patients with lung cancer. To assess whether or not miR-99b has a functional role in lung cancer, we determined the expression of miR-99b and fibroblast growth factor receptor 3 (FGFR3), which is a predicted target of miR-99b in public algorithms in human lung cancer tissues. miR-99b was downregulated and FGFR3 was upregulated in lung cancer patients. We demonstrated that the overexpression of miR-99b induced a reduction in FGFR3 expression and confirmed the target specificity between miR-99b and the FGFR3 3′-untranslated region by luciferase reporter assay. In addition, the growth rate in miR-99b precursor-treated cells was lower compared to the negative controls. Taken together, these results suggest that miR-99b may be a tumor suppressor through the downregulation of FGFR3. miR-99b may be a potent tumor suppressor and may be a potential therapeutic tool for patients with lung cancer.

Background: Cyclooxygenase-2 (COX-2) plays an important role in the development of lung cancer. DNA sequence variations in theCOX-2gene may lead to altered COX-2 production and/or activity, and so they cause inter-individual differences in the susceptibility to lung cancer. To test this hypothesis, we investigated the association between the8473T>Cpolymorphism in the 3'-untranslated region of theCOX-2gene and the risk of lung cancer in a Korean population.Methods: TheCOX-2genotypes were determined using PCR-based primer-introduced restriction analysis in 582 lung cancer patients and in 582 healthy controls that were frequency-matched for age and gender.Results: The distribution of theCOX-2 8473T>Cgenotypes was not significantly different between the overall lung cancer cases and the controls. However, when the cases were categorized by the tumor histology, the combined8473 TC+CCgenotype was associated with a significantly decreased risk of adenocarcinoma as compared with the8473 TTgenotype (adjusted OR = 0.64; 95% CI = 0.46–0.90,P= 0.01). On the stratification analysis, the protective effect of the combined8473 TC+CCgenotype against adenocarcinoma was statistically significant in the males, older individuals and ever-smokers (adjusted OR = 0.59; 95% CI = 0.39–0.91,P= 0.02; adjusted OR = 0.55; 95% CI = 0.33–0.93,P= 0.03; and adjusted OR = 0.57; 95% CI = 0.37–0.87,P= 0.01, respectively).Conclusion: These findings suggest that theCOX-2 8473T>Cpolymorphism could be used as a marker for the genetic susceptibility to adenocarcinoma of the lung.

During cancer progression, some tumor cells show changes in their plasticity by morphological and phenotypical conversions, as an expression of mesenchymal markers and loss of epithelial markers, collectively referred to as epithelial-mesenchymal transition (EMT). EMT has been increasingly recognized as a critical phenomenon in lung cancer progression. The goal of this study was to identify microRNAs involved in lung cancer progression. A microarray and qRT-PCR were performed to investigate the miRNA expression profiles in mesenchymal-like lung cancer cells. The role of miR‑146a in lung cancer progression was measured by invasion and migration assays in vitro. Bioinformatics and luciferase report assays were used to identify the target of miR‑146a. The expression of miR‑146a was reduced in mesenchymal-like lung cancer cell lines. The overexpression of miR‑146a induced a marked reduction of the mesenchymal marker and increase the epithelial marker in lung cancer cell lines. Moreover, the overexpression of miR‑146a suppressed lung cancer cell migration and invasion. Co-treatment with miR‑146a and gefitinib treatment showed a significant reduction of invasion in the resistant lung cancer cells induced by EMT. The expression of miR‑146a was downregulated in advanced lung cancer tissues. Insulin receptor substrate 2 (IRS2), an adaptor protein that modulates normal growth, metabolism, survival, and differentiation, was identified as a target of miR‑146a. miR‑146a regulated the expression of IRS2 at the mRNA and protein levels. These data demonstrate for the first time that miR‑146a suppresses lung cancer progression by repressing IRS2 expression. This provides new insight into the post-transcriptional regulation of lung cancer progression by miRNAs, a potential approach for the treatment of lung cancer.

Cheong HS, et al. J Korean Med Sci. 2022 Feb;37(6):e49. https://doi.org/10.3346/jkms.2022.37.e49