Dataset Information

MiR-218-5p restores sensitivity to gemcitabine through PRKCE/MDR1 axis in gallbladder cancer.

ABSTRACT: Gallbladder cancer (GBC) is one of the most common malignancy of the biliary tract characterized by its high chemoresistant tendency. Although great progresses have been made in recent decades for treating many cancers with anticancer drugs, effective therapeutics methods for anti-GBC are still lacking. Therefore, investigations into identifying the mechanisms underlying the drug resistance of GBC are greatly needed. In this study, we show that miR-218-5p plays a critical role in gemcitabine resistance of GBC. miR-218-5p levels were significantly lower in GBC than adjacent non-cancer tissues, and which were also associated with patient prognosis. While miR-218-5p overexpression abrogated gemcitabine resistance of GBC cells, silencing of which exhibited the opposite effects. Via six microRNA targets prediction algorithms, we found that PRKCE is a potential target of miR-218-5p. Moreover, miR-218-5p overexpression repressed the luciferase activity of reporter constructs containing 3'-UTR of PRKCE and also reduced PRKCE expression. Further studies revealed that miR-218-5p promotes sensitivity of gemcitabine by abolishing PRKCE-induced upregulation of MDR1/P-gp. Taken together, our results imply that an intimate correlation between miR-218-5p and PRKCE/MDR1 axis abnormal expression is a key determinant of gemcitabine tolerance, and suggest a novel miR-218-5p-based clinical intervention target for GBC patients.

SUBMITTER: Wang H

PROVIDER: S-EPMC5520703 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

miR-218-5p restores sensitivity to gemcitabine through PRKCE/MDR1 axis in gallbladder cancer.

Wang Hui H Zhan Ming M Xu Sun-Wang SW Chen Wei W Long Man-Mei MM Shi Yong-Heng YH Liu Qiang Q Mohan Man M Wang Jian J

Cell death & disease 20170511 5

Gallbladder cancer (GBC) is one of the most common malignancy of the biliary tract characterized by its high chemoresistant tendency. Although great progresses have been made in recent decades for treating many cancers with anticancer drugs, effective therapeutics methods for anti-GBC are still lacking. Therefore, investigations into identifying the mechanisms underlying the drug resistance of GBC are greatly needed. In this study, we show that miR-218-5p plays a critical role in gemcitabine res ...[more]

PMID: 28492560

Similar Datasets

Project description:Kidney renal clear cell carcinoma (KIRC or ccRCC) is the most notorious subtype of renal cell carcinoma for its poor prognosis. Mounting evidence has highlighted the key role of PRKCE in the initiation and development of several types of human cancer, including kidney renal clear cell carcinoma (KIRC). However, the mechanism of PRKCE aberrant expression and the specific clinical correlation of PRKCE expression with immune cell infiltration in KIRC remains elusive. Therefore, we analyzed the relationship between PRKCE and KIRC using many databases, including Oncomine, TCGA, GTEx, TIMER, and GEO. We found that PRKCE decreased in KIRC tumor tissue compared to normal tissue. The Kaplan-Meier Plotter analysis and Univariate and Multivariate Cox analyses were used to evaluate the association between PRKCE and clinicopathological variables and prognosis. Low PRKCE expression was associated with poor survival and histologic grade, T stage, pathologic stage, and M stage. Besides, the C-indexes and calibration plots of the nomogram based on multivariate analysis showed an effective predictive performance for KIRC patients. In addition, PRKCE may be positively correlated with inflammation and negatively correlated with proliferation, metastasis, and invasion as identified by CancerSEA. Moreover, overexpression of PRKCE suppressed ACHN and Caki-1 cell proliferation, migration, and invasion in vitro. Additionally, methylation level data acquired from UALCAN, DiseaseMeth, CCLE, LinkedOmics, and MEXPRESS was used to investigate the relationship between PRKCE expression and PRKCE methylation level. Furthermore, upstream potential miRNA predictions were further performed to explore the mechanism of PRKCE decreased expression in KIRC using multiple online databases available on publicly assessable bioinformatics platforms. High PRKCE methylation levels and hsa-miR-21-5p may contribute to PRKCE low expression in KIRC. Finally, an analysis of immune infiltration indicated that PRKCE was associated with immune cell infiltration. Importantly, PRKCE may affect prognosis partially by regulating immune infiltration in KIRC. In summary, PRKCE may serve as a novel prognostic biomarker reflecting immune infiltration level and a novel therapeutic target in KIRC.

Project description:BackgroundPancreatic cancer is a highly lethal malignancy with poor prognosis. Anillin (ANLN), an actin binding protein, is upregulated and plays an important role in many malignant tumors. However, the precise role of ANLN in pancreatic cancer remains unclear.MethodsThe expression of ANLN and its association with pancreatic cancer patient survival were analyzed using an online database and confirmed by immunohistochemistry. The ANLN protein expression in pancreatic cancer cell lines was detected by Western blot. Cell proliferation, colony formation and transwell assays in vitro and in vivo tumor growth were used to determine the role of ANLN in pancreatic cancer. Gene expression microarray analysis and a series of in vitro assays were used to elucidate the mechanisms of ANLN regulating pancreatic cancer progression.ResultsWe found that the ANLN expression was significantly upregulated in pancreatic cancer tissues and cell lines. The high expression of ANLN was associated with tumor size, tumor differentiation, TNM stage, lymph node metastasis, distant metastasis and poor prognosis in pancreatic cancer. ANLN downregulation significantly inhibited cell proliferation, colony formation, migration, invasion and tumorigenicity in nude mice. Meanwhile, we found that ANLN knockdown inhibited several cell-cell adhesion related genes, including the gene encoding LIM and SH3 protein 1 (LASP1). LASP1 upregulation partially reversed the tumor-suppressive effect of ANLN downregulation on pancreatic cancer cell progression. Moreover, we found that ANLN downregulation induced the expression of miR-218-5p which inhibited LASP1 expression through binding to its 3'UTR. We also found that ANLN-induced enhancer of zeste homolog 2 (EZH2) upregulation was involved in regulating miR-218-5p/LASP1 signaling axis. EZH2 upregulation or miR-218-5p downregulation partially reversed the tumor-suppressive effect of ANLN downregulation on pancreatic cancer cell progression.ConclusionANLN contributed to pancreatic cancer progression by regulating EZH2/miR-218-5p/LASP1 signaling axis. These findings suggest that ANLN may be a candidate therapeutic target in pancreatic cancer.

Dataset Information

MiR-218-5p restores sensitivity to gemcitabine through PRKCE/MDR1 axis in gallbladder cancer.

Publications

miR-218-5p restores sensitivity to gemcitabine through PRKCE/MDR1 axis in gallbladder cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets