Search

Abstract Background Accumulating evidence indicates that dysregulation of miR-182-5p can serve as diagnostic and prognostic biomarkers for some cancers, whereas the role of miR-182-5p has not been explored in nasopharyngeal carcinoma (NPC). Our study aims to elucidate the biological function of miR-182-5p in NPC and the potential molecular mechanism involved. Methods Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to determine miR-182-5p expression in NPC primary tissues and cell lines. Immunohistochemistry (IHC) for ZFP36L1 was conducted in NPC samples. Western blot was used to evaluate protein expression in cell lines. A series of functional assays were carried out to evaluate the roles of miR-182-5p and ZFP36L1 in tumor development and progression of NPC. Bioinformatics tools and luciferase reporter assays were utilized to identify the potential mechanisms of action. Moreover, rescue experiments were applied to explore whether ZFP36L1 mediated the effects of miR-182-5p in NPC. Results Up-regulation of miR-182-5p was significantly associated with tumor development and poor prognosis in patients with NPC. Functional study demonstrated that miR-182-5p overexpression enhanced, whereas suppression of miR-182-5p impeded NPC cell proliferation, migration, tumorigenesis and metastasis. Mechanistically, miR-182-5p interacted with ZFP36L1 at two sites in its 3′ un-translated region (UTR) and repressed ZFP36L1 expression in NPC. Consistently, an inverse correlation was observed between the expression levels of miR-182-5p and ZFP36L1 using clinical NPC tissues, and down-regulation of ZFP36L1 in NPC predicts poor survival. Furthermore, overexpression of miR-182-5p in NPC was partly attributable to the transcriptional activation effect induced by hypoxia-inducible factor 1α (HIF-1α). Conclusions Our data suggests that miR-182-5p facilitates cell proliferation and migration in NPC through its ability to down-regulate ZFP36L1 expression, and that the HIF-1α/miR-182-5p/ZFP36L1 axis may serve as a novel therapeutic target in the management of NPC.

Abstract Background Oral squamous cell carcinoma (OSCC) is a more common cancer in the world. Emerging evidence suggests that circular RNAs (circRNAs) participate in the progression of OSCC. However, the role of circ_0000140 in OSCC is still unknown. Methods The expression of circ_0000140 and microRNA-182-5p (miR-182-5p) were assessed by quantitative real-time polymerase chain reaction (qRT-PCR). Also, cell proliferation, migration and invasion were measured by colony formation and transwell assays, respectively. Western blot (WB) analysis was used to test the levels of proliferation, metastasis and glycolysis metabolism-related proteins as well as cell division cycle 73 (CDC73) protein. Further, the extracellular acidification rate (ECAR) of cells was detected by the Seahorse XF Extracellular Flux Analyzer. The lactate acid level of cells was tested by Lactate Assay Kit. Moreover, dual-luciferase reporter was used to verify the interaction between miR-182-3p and circ_0000140 or CDC73, and RNA immunoprecipitation (RIP) assay was employed to further confirm the relationship between miR-182-3p and circ_0000140. In addition, mice xenograft models were built to measure the effect of circ_0000140 on OSCC tumor growth in vivo. Results Circ_0000140 was lowly expressed in OSCC, and its overexpression hindered proliferation, migration, invasion and glycolysis metabolism in OSCC cells. MiR-182-5p could be sponged by circ_0000140, and its mimic could invert the suppression of circ_0000140 overexpression on OSCC progression. CDC73 could be targeted by miR-182-3p, and its silencing could reverse the inhibition of miR-182-3p inhibitor on OSCC progression. Further, overexpressed circ_0000140 reduced the OSCC tumor growth in vivo. Conclusions Circ_0000140 might play an anti-cancer role in OSCC, which provided a novel target for clinical therapy of OSCC.

Background: Accumulating evidence indicates that dysregulation of miR-182-5p can serve as diagnostic and prognostic biomarkers for some cancers, whereas the role of miR-182-5p has not been explored in nasopharyngeal carcinoma (NPC). Our study aims to elucidate the biological function of miR-182-5p in NPC and the potential molecular mechanism involved. Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to determine miR-182-5p expression in NPC primary tissues and cell lines. Immunohistochemistry (IHC) for ZFP36L1 was conducted in NPC samples. Western blot was used to evaluate protein expression in cell lines. A series of functional assays were carried out to evaluate the roles of miR-182-5p and ZFP36L1 in tumor development and progression of NPC. Bioinformatics tools and luciferase reporter assays were utilized to identify the potential mechanisms of action. Moreover, rescue experiments were applied to explore whether ZFP36L1 mediated the effects of miR-182-5p in NPC. Results: Up-regulation of miR-182-5p was significantly associated with tumor development and poor prognosis in patients with NPC. Functional study demonstrated that miR-182-5p overexpression enhanced, whereas suppression of miR-182-5p impeded NPC cell proliferation, migration, tumorigenesis and metastasis. Mechanistically, miR-182-5p interacted with ZFP36L1 at two sites in its 3′ un-translated region (UTR) and repressed ZFP36L1 expression in NPC. Consistently, an inverse correlation was observed between the expression levels of miR-182-5p and ZFP36L1 using clinical NPC tissues, and down-regulation of ZFP36L1 in NPC predicts poor survival. Furthermore, overexpression of miR-182-5p in NPC was partly attributable to the transcriptional activation effect induced by hypoxia-inducible factor 1α (HIF-1α). Conclusions: Our data suggests that miR-182-5p facilitates cell proliferation and migration in NPC through its ability to down-regulate ZFP36L1 expression, and that the HIF-1α/miR-182-5p/ZFP36L1 axis may serve as a novel therapeutic target in the management of NPC. [ABSTRACT FROM AUTHOR]

Abstract Background Human bladder cancer is one of the common malignant tumors, and it mainly occurs in men. miR-182-5p, a member of miR-183 family, acts as tumor suppressor or oncogene in various kinds of tumors. In this study, we first investigate that the absence of miR-182-5p in human bladder cancer promotes tumor growth by regulating the expression of Cofilin 1, an actin modulating-protein. Methods Human bladder tumor tissue specimens were collected to detect the expression of miR-182-5p and Cofilin 1 by qRT-PCR. Luciferase activity assay was performed to demonstrate the regulation of Cofilin 1 mRNA 3′UTR by miR-182-5p. Then, cell experiments were performed to analysis the effect of miR-182-5p/Cofilin 1 pathway on tumor cell proliferation, migration, invasion and colony forming efficiency. Finally, xenograft tumor models were established to evaluate the role of miR-182-5p in tumorigenesis abilities in vivo. Results qRT-PCR and Western blotting analysis showed that Cofilin 1 expression was up-regulated in both bladder cancer tissues and cell lines compared with normal. Luciferase activity assay showed that miR-182-5p specifically targets Cofilin 1 mRNA 3′UTR and represses the expression of Cofilin 1. Also, miR-182-5p inhibited bladder tumor cell proliferation, migration, invasion and colony forming efficiency. Furthermore, xenograft tumor model assay showed that miR-182-5p plays a negative role in bladder cancer tumorigenesis abilities in vivo. Conclusion Present results suggest that miR-182-5p could inhibit human bladder tumor growth by repressing Cofilin 1 expression. Our findings may provide a new horizon for exploring therapeutic target of bladder cancer.

Background: Oral squamous cell carcinoma (OSCC) is a more common cancer in the world. Emerging evidence suggests that circular RNAs (circRNAs) participate in the progression of OSCC. However, the role of circ_0000140 in OSCC is still unknown. Methods: The expression of circ_0000140 and microRNA-182-5p (miR-182-5p) were assessed by quantitative real-time polymerase chain reaction (qRT-PCR). Also, cell proliferation, migration and invasion were measured by colony formation and transwell assays, respectively. Western blot (WB) analysis was used to test the levels of proliferation, metastasis and glycolysis metabolism-related proteins as well as cell division cycle 73 (CDC73) protein. Further, the extracellular acidification rate (ECAR) of cells was detected by the Seahorse XF Extracellular Flux Analyzer. The lactate acid level of cells was tested by Lactate Assay Kit. Moreover, dual-luciferase reporter was used to verify the interaction between miR-182-3p and circ_0000140 or CDC73, and RNA immunoprecipitation (RIP) assay was employed to further confirm the relationship between miR-182-3p and circ_0000140. In addition, mice xenograft models were built to measure the effect of circ_0000140 on OSCC tumor growth in vivo. Results: Circ_0000140 was lowly expressed in OSCC, and its overexpression hindered proliferation, migration, invasion and glycolysis metabolism in OSCC cells. MiR-182-5p could be sponged by circ_0000140, and its mimic could invert the suppression of circ_0000140 overexpression on OSCC progression. CDC73 could be targeted by miR-182-3p, and its silencing could reverse the inhibition of miR-182-3p inhibitor on OSCC progression. Further, overexpressed circ_0000140 reduced the OSCC tumor growth in vivo. Conclusions: Circ_0000140 might play an anti-cancer role in OSCC, which provided a novel target for clinical therapy of OSCC. [ABSTRACT FROM AUTHOR]