RESUMO
Long non-coding RNA homeobox A11-antisense RNA (HOXA11-AS) has been implicated in cisplatin (DDP) resistance in multiple types of cancer. The purpose of the present study was to investigate the role of HOXA11-AS in DDP-resistant nasopharyngeal carcinoma (NPC) cells. The expression levels of HOXA11-AS were examined using reverse transcription-quantitative PCR. Cell viability was measured using a Cell Counting Kit-8 assay, and a TUNEL assay was utilized to assess cell apoptosis. The expression levels of apoptosis-related factors (Bax and Bcl-2) were detected by western blot analysis. The interaction between microRNA-98 (miR-98) and HOXA11-AS or pre-B-cell leukemia homeobox 3 (PBX3) was demonstrated using bioinformatics analysis, dual-luciferase reporter assays and RNA immunoprecipitation assays. HOXA11-AS and PBX3 expressions levels were upregulated, whereas miR-98 levels were downregulated in DDP-resistant NPC tissues. Patients with NPC with high HOXA11-AS expression had a low survival rate. Knockdown of HOXA11-AS enhanced the DDP sensitivity of DDP-resistant NPC (5-8F/DDP and SUNE1/DDP) cells, which was demonstrated by the accelerated apoptosis. In addition, HOXA11-AS inhibited the expression levels of miR-98 through direct interaction. Furthermore, miR-98 inhibition counteracted the inductive effect of HOXA11-AS-knockdown on the DDP sensitivity of NPC cells. PBX3 was a target of miR-98 and was positively modulated by HOXA11-AS. Overexpression of PBX3 reversed the suppressive effect of HOXA11-AS silencing on the DDP resistance of NPC cells. The data demonstrated that HOXA11-AS enhanced DDP resistance in NPC via the miR-98/PBX3 axis, providing a potential therapeutic target for patients with DDP-resistant NPC.
RESUMO
BACKGROUND: Cisplatin (DDP) resistance has become an obstacle to chemotherapy for nasopharyngeal carcinoma (NPC) patients. Recent evidences indicate that long noncoding RNAs (lncRNAs) are involved in tumorigenesis and chemoresistance. However, the potential role of lncRNAs in NPC progression remains largely unknown. METHODS: First, lncRNA expression profiling in NPC was performed via microarray analysis. To explore the involvement of DLEU1 in DDP resistance, loss-of-function experiments were employed in vitro and in vivo. Bioinformatics analysis, luciferase reporter assay, qRT-PCR, and Western blot assays were used to investigate the underlying mechanisms. RESULTS: Here, we identified 153 differentially expressed lncRNAs. Among them, DLEU1 was remarkably up-regulated in NPC tissues and associated with worse outcome. Knock-down of DLEU1 could sensitize NPC cells to DDP in vitro and in vivo. Further investigations revealed that DLEU1 positively regulated BIRC6 expression via its competing endogenous RNA (ceRNA) activity on miR-381-3p. We also observed that BIRC6 overexpression or miR-381-3p silence could significantly reverse DLEU1-dependent DDP resistance. CONCLUSION: Our data suggest that DLEU1 acts as an oncogene to promote DDP resistance and BIRC6 expression in NPC through interacting with miR-381-3p, which may help to develop new strategy against NPC chemoresistance.
RESUMO
Controlled tuning of interface adhesion is crucial to a broad range of applications, such as space technology, micro-fabrication, flexible electronics, robotics, and bio-integrated devices. Here, we show a robust and predictable method to continuously regulate interface adhesion by exciting the mechanical micro-vibration in the adhesive system perpendicular to the contact plane. An analytic model reveals the underlying mechanism of adhesion hysteresis and dynamic instability. For a typical PDMS-glass adhesion system, the apparent adhesion strength can be enhanced by 77 times or weakened to 0. Notably, the resulting adhesion switching timescale is comparable to that of geckos (15 ms), and such rapid adhesion switching can be repeated for more than 2 × 107 vibration cycles without any noticeable degradation in the adhesion performance. Our method is independent of surface microstructures and does not require a preload, representing a simple and practical way to design and control surface adhesion in relevant applications.
