Long noncoding RNA DSCR8 promotes the proliferation of liver cancer cells and inhibits apoptosis via the miR-22-3p/ARPC5 Axis.

Emerging evidence shows that long noncoding RNAs (lncRNAs) play a vital role in the tumorigenesis and development of cancer, implying that some lncRNAs could be potential therapeutic targets. In this study, we employed Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases to construct a ceRNA network by bioinformatic analysis, and the Down syndrome critical region 8 (lncRNA_DSCR8)/miR-22-3p/actin-related protein 2/3 complex subunit 5 (ARPC5) axis was identified as a potential target in liver cancer (LC). Next, we found that DSCR8 is highly expressed in LC cell lines Hep3B and Huh7. In addition, sh-DSCR8 inhibits cell proliferation and promotes cell apoptosis. Furthermore, we certified that DSCR8 serves as function as a sponge for miR-22-3p, while ARPC5 is a target gene of miR-22-3p, and the functions of DSCR8 promoting LC cell proliferation could be rescued by miR-22-3p. This study suggests that lncRNA_DSCR8 promotes LC progression and inhibits its apoptosis by regulating the miR-22-3p/ARPC5 axis, signifying that DSCR8 could be a novel therapeutic target for LC.

RAFT Polymerization of Semifluorinated Monomers Mediated by a NIR Fluorinated Photocatalyst.

Near-infrared (NIR) light plays an increasingly important role in the field of photoinduced electron/energy transfer-reversible addition-fragmentation chain transfer (PET-RAFT) polymerization due to its unique properties. Yet, the NIR photocatalyst with good stability for PET-RAFT polymerization remains promising. Here, a strategy of NIR PET-RAFT polymerization of semifluorinated monomers using fluorophenyl bacteriochlorin as a photocatalyst with strong absorption at the NIR light region (710-780 nm) is reported. In which, the F atoms are used to modify reduced tetraphenylporphyrin structure with enhanced photostability of photocatalyst. Under the irradiation of NIR light (λmax = 740 nm), the PET-RAFT polymerization of semifluorinated methylacrylic monomers presents living/control characteristics and temporal modulation. By the PET-RAFT polymerization-induced self-assembly (PISA) strategy, stable fluorine-containing micelles are constructed in various solvents. In addition, the fluorinated hydrophobic surface is fabricated via a surface-initiated PET-RAFT (SI-PET-RAFT) polymerization using silicon wafer bearing RAFT agents with tunable surface hydrophobicity. This strategy not only enlightens the application of further modified compounds based on porphyrin structure in photopolymerization, but also shows promising potential for the construction of well-defined functional fluoropolymers.

Tumor-derived exosomal miRNA-141 promote angiogenesis and malignant progression of lung cancer by targeting growth arrest-specific homeobox gene (GAX).

Previous researches have suggested that exosomal miRNA-141 has association with metastatic lung cancer, however, its role and regulatory mechanism require further study. In this study, exosomes were isolated from lung cancer patients and normal human serum and identified. We found that the expression of miRNA-141 was up-regulated in the lung cancer serum exosomes compared with the normal serum exosomes. When the exosomes were extracted for co-culture with HUVECs, they were absorbed and distributed around the nucleus by confocal microscopy. Moreover, exosomal miRNA-141 from A549 significantly not only promoted the migration and invasion of A549 but also increased the cell proliferation, tube formation of HUVECs. In order to reveal the mechanism of exosomal miRNA-141, bioinformatics analysis revealed that miRNA-141 targeted the binding of Growth arrest-specific homeobox gene (GAX) in the 3'UTR region, and confirmed by MS2-RIP assay and dual-luciferase assay. Exosome miRNA-141 could down-regulate the expression of GAX. Taken together, our results demonstrate that tumor-derived exosomal miRNA-141 promote angiogenesis and malignant progression of lung cancer by targeting GAX. It provides a new possibility for the treatment of lung cancer.

miR-124-3p Regulates FGF2-EGFR Pathway to Overcome Pemetrexed Resistance in Lung Adenocarcinoma Cells by Targeting MGAT5.

OBJECTIVE: To investigate whether miR-124-3p regulates the fibroblast growth factor 2 (FGF2)-epidermal growth factor receptor (EGFR) pathway by targeting MGAT5 to affect the pemetrexed resistance in lung adenocarcinoma cells. METHODS: PC9-MTA and H1993-MTA anti-pemetrexed lung adenocarcinoma cell lines were constructed. The cell viability of anti-pemetrexed and parent lung adenocarcinoma cells was analyzed using MTS assay and reverse transcription PCR to determine the expression of miR-124-3p. CCK8 assay, colony formation assay, and flow cytometry were used to determine cells' proliferation and apoptosis. FGF2-EGFR signaling pathway-related proteins and MGAT5 protein expression were quantified by Western blotting. The target relationship between miR-124-3p and MGAT5 was verified by double luciferase assay. A nude mouse model with a transplanted tumor was established using the anti-pemetrexed lung adenocarcinoma cells. Tumor volume and weight were determined, and the apoptosis of tumor cells was observed. RESULTS: The half-maximal inhibitory concentration of pemetrexed in anti-pemetrexed lung adenocarcinoma cells was higher than that in parent lung adenocarcinoma cells, and the expression of miR-124-3p in the anti-pemetrexed cells was lower than that of the parent cells. In the miR-124-3p overexpression group, MGAT5 silencing group, and miR-124-3p+MGAT5 overexpression group, compared with the control group, the proliferation ability of cells and tumors was markedly reduced; their apoptosis rates were increased significantly; expression levels of FGF2 and p-EGFR/EGFR were decreased; and the growth rate and tumor volume and mass were reduced; however, the opposite results were obtained in the miR-124-3p silencing group (p<0.05). CONCLUSION: miR-124-3p may inhibit the FGF2-EGFR pathway by targeting MGAT5 to decrease pemetrexed resistance in lung adenocarcinoma cells.

Analysis of mutation of the c-Kit gene and PDGFRA in gastrointestinal stromal tumors.

The aim of the present study was to investigate mutation status of the c-Kit gene (KIT) and PDGFRA in patients with a gastrointestinal stromal tumor (GIST). In total, 93 patients with a GIST were included in the study, in which polymerase chain reaction amplification and gene sequencing were used to detect the sequences of exons 9, 11, 13 and 17 in KIT and exons 12 and 18 in PDGFRA. KIT mutations were detected in 64 cases (68.82%), of which exon 11 mutations were detected in 56 cases (60.22%), exon 13 mutations were detected in three cases (3.23%) and one case (1.08%) was shown to have a mutation in exon 17. The most common mutation in exon 11 was a deletion, which accounted for 55.36% (31/56) of the cases, followed by a point mutation observed in 26.79% (15/56) of the cases, while an insertion (tandem repeats) was identified in 14.29% (8/56) of the cases, and 3.57% (2/56) of the exon 11 mutations were deletions associated with a point mutation. The majority of the mutations were heterozygous, with only a few homozygous mutations. Mutational analysis revealed the mutations to be more concentrated in the classic hot zone at the 5'-end, followed by the tandem repeat frame at the 3'-end. In four cases, a mutation was detected in exon 18 of PDGFRA, of which one was associated with a mutation in KIT. The remaining three cases (10.34%, 3/29) were not associated with mutations in KIT and accounted for 37.5% (3/8) of the CD117-negative GIST cases. Therefore, the majority of the GIST cases were characterized by mutations in KIT or PDGFRA, which were directly associated with the disease. Pairs of different mutations in the same exon of KIT, or KIT mutations coupled with pairs of mutations in PDGFRA, were detected in a small number of patients. Imatinib is a small molecule tyrosine kinase inhibitor and is the first line targeted treatment for GIST, resulting in markedly improved survival rates. Thus, gene mutation genotyping may provide inspiration and guidance for imatinib-based targeted cancer therapy.

Association between EML4-ALK fusion gene and thymidylate synthase mRNA expression in non-small cell lung cancer tissues.

This study aimed to investigate the association of the mRNA expression of the echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) fusion gene with that of thymidylate synthase (TYMS) in non-small cell lung cancer (NSCLC) tissues. Quantitative polymerase chain reaction was used to detect the expression of EML4-ALK fusion gene and TYMS mRNA in 257 cases of NSCLC. The positive rate of EML4-ALK fusion gene was 4.28% in the NSCLC tissues (11/257), and was higher in nonsmokers than in smokers (P<0.05); TYMS mRNA expression was detected in 63.42% (163/257) of cases. An association of the EML4-ALK fusion gene with TYMS expression was detected; a low expression level of TYMS mRNA was observed more frequently when the EML4-ALK fusion gene was present than when it was not detected (P<0.05). In conclusion, patients positive for the EML4-ALK fusion gene in NSCLC tissues are likely to have a low expression level of TYMS, and may benefit from the first-line chemotherapy drug pemetrexed.

Association between epidermal growth factor receptor mutations and the expression of excision repair cross-complementing protein 1 and ribonucleotide reductase subunit M1 mRNA in patients with non-small cell lung cancer.

The present study aimed to investigate the association between epidermal growth factor receptor (EGFR) gene mutations and excision repair cross-complementing protein 1 (ERCC1) and ribonucleotide reductase subunit M1 (RRM1) mRNA expression in non-small cell lung cancer (NSCLC) tissue. The quantitative polymerase chain reaction was used to detect EGFR mutations, and ERCC1 and RRM1 mRNA expression in 257 cases of NSCLC. In the NSCLC samples the EGFR mutation rate was 49.03% (126/257). The rate was higher in females and non-smoking patients (P<0.05). High expression of ERCC1 mRNA was observed in 47.47% of the samples (122/257), while a high RRM1 mRNA expression was observed in 61.87% of the samples (159/257). In comparison with patients with NSCLC without EGFR mutations, patients with EGFR mutations had significantly lower levels of ERCC1 mRNA expression (P<0.05); however, EGFR mutations and expression levels of RRM1 mRNA were not correlated in NSCLC tissues (P>0.05). In addition, ERCC1 mRNA expression was not correlated with the expression levels of RRM1 mRNA (P>0.05). In conclusion, patients with NSCLC with EGFR mutations tend to have a low expression of ERCC1 mRNA and may potentially benefit from platinum-based chemotherapy.

Two functional polymorphisms in microRNAs and lung cancer risk: a meta-analysis.

MicroRNAs are involved in several biological processes including cell apoptosis and proliferation, stress resistance, and fat metabolism, and act as tumor suppressors by malignant transformation of human cells. The aim of this study was to identify the associations of single nucleotide polymorphisms (SNPs) rs11614913 and rs3746444 with lung cancer risk. In this meta-analysis with 2,219 cases and 2,232 controls for SNP rs11614913 and 1,685 cases and 1,690 controls for SNP rs3746444, we summarized five case-control studies by searching databases of PubMed, EMBASE, and Chinese National Knowledge Infrastructure (CNKI). Lung cancer risk associated with the two SNPs was estimated by odd ratios (ORs) with 95% confidence intervals (CIs). SNP rs11614913 (OR 0.88, 95% CI 0.78-1.00 for TT vs. CT + CC) was found to be potentially associated with a decreased risk of lung cancer. However, we found no association between SNP rs3746444 and lung cancer risk. In the subgroup analysis by ethnicity, a negative association was also observed in Asians for SNP rs11614913, but a nonsignificant association for SNP rs3746444. Our meta-analysis provides evidence for potential protective effects on lung cancer risk associated with SNP rs11614913, particularly in Asian populations. Further, larger studies are necessary to validate the findings.