Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P42574 (caspase-3)
 45,978 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Drug resistance to platinum limited therapeutic options for oral squamous cell carcinoma (OSCC). In the current study, we investigated the role of lncRNA HOMEOBOX A11 (HOXA11) antisense RNA (HOXA11-AS) in OSCC resistance to cisplatin (CDDP). We used clinical tissues and OSCC cell lines and induced CDDP resistance in OSCC cells. Gain and loss of function were performed in OSCC-resistant cells. Xenograft mice were also established. HOXA11-AS expression was increased in OSCC clinical tissues and cell lines and upregulated in CDDP-resistant cells. Upregulation of HOXA11-AS promoted proliferation in CDDP-sensitive cells and inhibited CDDP-induced cytotoxicity. In contrast, downregulation of HOXA11-AS decreased proliferation in CDDP-resistant cells and increased CDDP-induced cytotoxicity. Knockdown of HOXA11-AS inhibited the tumor growth in xenograft mice injected by CDDP. Downregulation of HOXA11-AS increased apoptosis and caspase 3 activities in CDDP-resistant OSCC cells. Bioinformatics, reporter assay, and loss and gain of function assay indicated that HOXA11-AS and miR-214-3p could negatively regulate each other. miR-214-3p was decreased in OSCC clinical tissues and cell lines. We further revealed that proto-oncogene serine/threonine-protein kinase (PIM1) was the target of miR-214-3p. PIM1 expression could be negatively regulated by miR-214-3p and positively regulated by HOXA11-AS. Inhibition of PIM1 suppressed anti-miR-214-3p-induced increase of cell proliferation and decrease of apoptosis. In summary, HOXA11-AS was identified to facilitate CDDP-resistance in OSCC and miR-214-3p/PIM1 was found to be the downstream target of HOXA11-AS. The findings highlight the importance of HOXA11-AS/miR-214-3p/PIM1 axis in the drug resistance of OSCC and provide potential targets for improving chemotherapy of OSCC.
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PMID:LncRNA HOXA11-AS Promotes Proliferation and Cisplatin Resistance of Oral Squamous Cell Carcinoma by Suppression of miR-214-3p Expression. 3127 88

Glioma is an aggressive nervous system tumor with poor prognosis. Although the therapeutic strategies to overcome glioma have been improved largely recent years, the potential mechanism of its carcinogenesis remains largely unclear. The present study aimed to investigate the role of long non-coding RNA HOMEOBOX A11 antisense RNA (lncRNA HOXA11-AS) in glioma, and further to explore the underlying mechanism. We forst detected the level of lncRNA HOXA11-AS and microRNA-125a (miR-125a) in glioma tissues and human glioma U251 cells using quantitative real time polymerase chain reaction (qRT-PCR). Then, effect of lncRNA HOXA11-AS silencing on U251 cell migration, invasion, proliferation, and apoptosis was determined. Meanwhile, the expression of caspase-3/8/9 and several tumor-related genes was measured by Western blotting and qRT-PCR. Dual luciferase activity assay was used to confirm the targeting relationship between lncRNA HOXA11-AS and miR-125a. Results indicated that lncRNA HOXA11-AS was significantly increased in U251 cells and positively correlated with glioma World Health Organization (WHO) grade in glioma tissues. lncRNA HOXA11-AS silencing could inhibit cell migration, invasion, proliferation, and promote apoptosis, while up-regulate the expression of caspase-3/8/9 and Bax, inhibit the expression of Bcl-2 and gab2 in U251 cells. miR-125a inhibitor could partially reverse these effects of lncRNA HOXA11-AS silencing on U251 cells. In vivo assays also indicated that lncRNA HOXA11-AS inhibitor could inhibit glioma growth in vivo by regulating the expression of miR-125a. In conclusion, we revealed that lncRNA HOXA11-AS acted as an oncogene in glioma via interacting with miR-125a and considered that lncRNA HOXA11-AS was a potential therapeutic target for glioma.
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PMID:Silencing of lncRNA HOXA11-AS inhibits cell migration, invasion, proliferation, and promotes apoptosis in human glioma cells via upregulating microRNA-125a: in vitro and in vivo studies. 3173 90