Background Non-small cell lung cancer (NSCLC) is a common malignant tumor in humans. Long non-coding RNA (lncRNA) involved in cancer progression has been reported frequently. The objective of this study was to investigate the role of lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and explore a novel mechanism in NSCLC development. Materials and Methods The expression of MALAT1, copper metabolism MURR1 domain-containing 8 ( COMMD8 ) and microRNA-613 (miR-613) was detected by quantitative real-time polymerase chain reaction (qRT-PCR). The protein levels of COMMD8, Cyclin D1, Ki67, B cell lymphoma/leukemia-2 (Bcl-2), Bcl-2 associated X protein (Bax), lactate dehydrogenase A (LDHA), CD63 and CD81 were determined by Western blot. Cell proliferation, the number of colonies and cell apoptosis were assessed by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT), colony formation and flow cytometry assays, respectively. Glycolysis was distinguished based on glucose consumption, lactate production and LDHA activity. The role of MALAT1 in vivo was verified by animal experiments. The relationship between miR-613 and MALAT1 or COMMD8 was predicted by the bioinformatics tool starbase and verified by dual-luciferase reporter assay. The exosomes were isolated using the corresponding kit and identified by transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA). Results MALAT1 and COMMD8 were aberrantly upregulated in NSCLC tissues and cells. MALAT1 or COMMD8 knockdown blocked cell proliferation, colony formation and glycolysis but accelerated cell apoptosis in vitro. Besides, MALAT1 knockdown reduced tumor growth in vivo. We found that miR-613 was a target of MALAT1, and miR-613 could bind to the 3ʹ untranslated region (3ʹUTR) of COMMD8 . MALAT1 regulated the expression of COMMD8 by absorbing miR-613. Moreover, the extracellular MALAT1 was transmitted by wrapping into exosomes. Conclusion MALAT1 promoted malignant activities of NSCLC cells through targeting miR-613/ COMMD8 axis, and exosome-mediated transfer of NSCLC might be a novel approach for NSCLC treatment.
Squamous cell carcinoma (SCC) is one of the most common skin cancers. In the present study, we explored the effects of depletion of murine double minute gene 2 (MDM2) together with overexpression of N-myc downstream-regulated gene 2 (NDRG2) on cutaneous SCC. In order to achieve high efficiency of gene knockdown and overexpression in SCC-13 cells, recombinant adenovirus carrying siMDM2 and NDRG2 expression construct was produced. We found Ad-siMDM2, Ad-NDRG2, and Ad-siMDM2-NDRG2 infections inhibit the growth of SCC-13 cells in vitro, and Ad-siMDM2-NDRG2 infection has the highest inhibitory effect. Subcutaneous injections of Ad-siMDM2, Ad-NDRG2, and Ad-siMDM2-NDRG2 into SCC-13 xenograft nude mice resulted in the reduction of tumor volume. Moreover, we found that apoptosis protein caspase 3 was up-regulated in the Ad-siMDM2-, Ad-NDRG2-, and Ad-siMDM2-NDRG2-treated groups. Our data indicate that the adenovirus-mediated MDM2 silencing and NDRG2 overexpression can synergistically inhibit local cancer cell proliferation, induce apoptosis, and further prevent metastases of SCC. Our study provides a promising method that can be further developed as a new therapeutic approach against SCC.
The present study aimed to explore the association between haptoglobin protein and mRNA expression and psoriasis. A total of 138 patients with psoriasis that were undergoing therapy at Linyi People's Hospital (Linyi, China) between January 2011 and January 2015 were enrolled in the present study. The mRNA expression levels of haptoglobin were detected by in situ hybridization; immunohistochemistry was used to detect haptoglobin protein expression; and double‑labeling immunofluorescence was used to count Langerhans cells; western blotting was also conducted to determine protein expression. A receiver operating characteristic (ROC) curve was generated to assess the diagnostic value of haptoglobin for psoriasis. Compared with the normal and negative control (NC) groups, the mRNA expression levels of haptoglobin were markedly increased in the experimental group (P<0.05). Haptoglobin protein expression was also markedly increased in the experimental group compared with in the normal and NC groups (P<0.05). Conversely, there was no significant difference in haptoglobin expression between the NC group and the normal group (P>0.05). The critical value of haptoglobin mRNA in the diagnosis of psoriasis was 2.93, and sensitivity and specificity were 91.3 and 73.6%, respectively. The area under the ROC curve was 0.883 [95% confidence interval (CI)=0.837‑0.929]. The critical value of haptoglobin protein in the diagnosis of psoriasis was 0.995, and sensitivity and specificity were 76.1 and 99.9%, respectively. The area under the ROC curve was 0.926 (95% CI=0.837‑0.929). The present study demonstrated that the mRNA and protein expression levels of haptoglobin were increased in patients with psoriasis. Haptoglobin mRNA and protein expression were closely associated with the occurrence of psoriasis; therefore, haptoglobin may be considered a promising novel clinical indicator for the diagnosis of psoriasis.
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