RESUMEN
The incidence rate of nasopharyngeal carcinoma (NPC) is the highest among the malignant tumors of otorhinolaryngology, posing a huge burden to public health. Long noncoding RNAs (lncRNAs) exert an important role in tumorigenesis and the progression of various cancers. The present study found that HOXC-AS1 was highly expressed in NPC and in NPC cell lines, suggesting a critical role of HOXC-AS1 in NPC progression. In addition, the abundance of HOXC-AS1 was negatively correlated with the prognosis of NPC. To molecularly dissect the mechanism of HOXC-AS1 in NPC progression, we knocked down the expression of HOXC-AS1 in HNE1 and C666-1 cells. Then, we employed CCK8, colony-formation experiment and Transwell to investigate how the cell performed when HOXC-AS1 was knocked down. It could be observed that HOXC-AS1 knockdown decreases cell proliferation, migration and invasion, but induces cell apoptosis in NPC. We found that HOXC-AS1 could sponge miR-4651 subsequently binding FOXO6 and inhibiting its expression. Therefore, HOXC-AS1/miR-4651/FOXO6 may form a competing endogenous RNA (ceRNA) network that promotes NPC progression. In conclusion, our study demonstrates that HOXC-AS1 promotes NPC progression by sponging miR-4651 and regulating FOXO6 expression, thus providing potential pharmaceutical targets for developing new NPC treatments.
Asunto(s)
Carcinogénesis/genética , Carcinogénesis/patología , Carcinoma/genética , Carcinoma/patología , Factores de Transcripción Forkhead/genética , Factores de Transcripción Forkhead/metabolismo , Regulación Neoplásica de la Expresión Génica/genética , MicroARNs/genética , MicroARNs/metabolismo , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/patología , ARN Largo no Codificante/fisiología , Regulación hacia Arriba/genética , Línea Celular Tumoral , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
MicroRNAs (miRNAs) belong to the subgroup of small noncoding RNAs, which typically serve as important gene regulators to participate in different biological events, such as tumor cell growth and apoptosis. Recent studies indicated microRNA-4651 (miR-4651) was involved in hepatocellular carcinoma (HCC) progression. The certain role of miRNA-4651 during the progression of HCC, however, remains unclear. Herein, we investigated the mRNA expression level of miR-4651 in HCC tissues and HCC cell lines and found miR-4651 was noticeably down-regulated compared with the normal liver tissues and QSG-7701 cell line, respectively. Then, miR-4561 overexpression obviously repressed the proliferation and promoted apoptosis in two HCC cell lines. Interestingly, we further identified that miR-4561 could directly interact with FOXP4 in HCC cells by using bio-informatic method and report assay. Moreover, forced expression of FOXP4 showed an opposite effect compared with miR-4561 in HCC cell lines. Hence, our findings strongly indicated that miR-4561 regulated the HCC cell growth and apoptosis mainly through targeting the FOXP4 genes. Clinically, the miR-4561/FOXP4 axis might be a potential target for therapeutic application of HCC patient treatment.
Asunto(s)
Carcinoma Hepatocelular/metabolismo , Proliferación Celular , Factores de Transcripción Forkhead/metabolismo , Neoplasias Hepáticas/metabolismo , MicroARNs/metabolismo , Apoptosis , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Factores de Transcripción Forkhead/genética , Regulación Neoplásica de la Expresión Génica , Células Hep G2 , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , MicroARNs/genética , Transducción de SeñalRESUMEN
Nonsense-mediated mRNA decay (NMD) is originally identified as a conserved RNA surveillance mechanism that rapidly degrades aberrant mRNA containing premature termination codons (PTCs). However, the molecular regulation mechanisms by which microRNAs inhibit NMD has not been well understood. Here we identified that miR-4651 participated in the NMD pathway by downregulating expression levels of SMG9. We provided evidences that (1) Overexpression of miR-4651 mimic significantly inhibited the expression of SMG9 (Pâ¯<â¯0.05); (2) NMD substrates genes, TBL2 and GADD45B were both increased at mRNA and protein expression levels when SMG9 was suppressed by siRNA, whereas decreased by SMG9 overexpression; (3) Expression of SMG9 was significantly increased but TBL2, GADD45B were significantly decreased when cells transfected with miR-4651 inhibitor (Pâ¯<â¯0.05). These results indicated that miR-4651 regulated NMD by targeting SMG9 mRNA. Our study highlights that miR-4651 represses NMD. miR-4651 targets SMG9 and represses the expression levels of SMG9. NMD activity is decreased additionally when SMG9 is inhibited. The present study provides evidence for microRNA/NMD regulatory mechanism.