Identification of biomarkers of intrahepatic cholangiocarcinoma via integrated analysis of mRNA and miRNA microarray data

Chang, Yaqing; Liu, Dan; Liu, Pengfei; Chen, Yajing; Yu, Huapeng; Zhang, Quan

doi:10.3892/mmr.2017.6123

Cited by 8 publications

(6 citation statements)

References 36 publications

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“…Various studies have demonstrated that the miRNA class of non-coding RNAs participate in tumor progression through regulating a series of target genes involved in tumor proliferation and metastasis (24). dysregulated expression or function of miRNAs has been demonstrated in a series of malignancies, including ccA (25). For example, miR-142-5p was shown to decrease the expression of phosphatase and tensin homolog and promote the progression of ccA (26).…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‑137 suppresses the proliferation, migration and invasion of cholangiocarcinoma cells by targeting WNT2B

et al. 2020

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It is widely known that abnormal regulation of microRNAs (miRNAs/miRs) may contribute to the occurrence or development of tumors. The objective of the present study was to elucidate the function and underlying mechanism of miR-137 in the progression of cholangiocarcinoma (ccA). The expression levels of miR-137 in ccA tissues and cell lines were measured using reverse transcription-quantitative PcR. The role of miR-137 in the proliferation of ccA cells was assessed using the cell counting Kit-8 assay, colony formation assay and cell cycle distribution analysis, while its effects on the migration and invasion of ccA cells were evaluated using Transwell assays. The function of miR-137 on ccA growth in vivo was also investigated using a xenograft mouse model. Furthermore, the association between miR-137 and Wnt family member 2B (WNT2B) was analyzed using bioinformatics, double luciferase assay and western blotting. It was verified that the expression of miR-137 was low in ccA tissues and cell lines, whereas increased expression of miR-137 significantly suppressed cell proliferation, decreased colony formation ability and induced G1 phase arrest. miR-137 overexpression suppressed the migration and invasion ability of TFK-1 and HuccT1 cells. Furthermore, the results of the xenograft mouse model assays revealed that miR-137 overexpression decreased tumor growth in vivo. The results of bioinformatics analysis and dual luciferase reporter assays demonstrated that WNT2B is directly regulated by miR-137. The expression of WNT2B and Wnt-pathway-related proteins was decreased when miR-137 was overexpressed. Restoring the expression of WNT2B notably reversed the inhibitory effect of miR-137 on CCA cells. Therefore, the findings of the present study demonstrated that miR-137 acts as a suppressor in ccA and inhibits ccA cell proliferation, migration and invasion through suppressing the expression of WNT2B.

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Section: Discussionmentioning

confidence: 99%

MicroRNA‑137 suppresses the proliferation, migration and invasion of cholangiocarcinoma cells by targeting WNT2B

et al. 2020

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“…miRNAs have been implicated in the pathogenesis of CCA 42 – 45 because upregulated miRNAs suggest an oncogenic role and downregulation of miRNAs may be suppressive, so dysregulated miRNAs are correlated with the adverse clinical features, diminished survival, and poor prognosis of CCA patients. 46 Selaru et al 36 proved that miR-21 was oncogenic by inhibiting PDCD4 and TIMP3 suppressor genes in the biliary tree. Wang et al 38 confirmed the functional and mechanistic links between miR-21 and tumor suppressor genes (such as PTPN14 and PTEN) in the pathogenesis of ICC, which influenced the proliferation and tumor progression in ICC.…”

Section: Discussionmentioning

confidence: 99%

Diagnostic and prognostic value of microRNAs in cholangiocarcinoma: a systematic review and meta-analysis

Sun¹,

Zhu²,

Wu³

et al. 2018

CMAR

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Background and aimSeveral dysregulated microRNAs (miRNAs) have been implicated in the pathogenesis of cholangiocarcinoma (CCA); however, small sample sizes and invariable research designs are limitations, hindering a thorough analysis of miRNAs as diagnostic and prognostic tools for CCA. This study aimed to systematically summarize the clinical value of miRNAs in human CCA both for all available miRNAs and single miRNA with multiple researches.MethodsPooled parameters included the area under the curve (AUC), sensitivity, specificity, and hazard ratios (HRs) to separately determine overall diagnostic and prognostic performance. Subgroup and sensitivity analyses were performed only in the event of heterogeneity. Thirty-four studies including 12 diagnostic studies and 22 prognostic studies were eligible for inclusion in this meta-analysis.ResultsWe observed that miR-21, miR-26, miR-483, miR-106a, miR-150, miR-192, and miR-194 were employed for distinguishing patients with CCA from healthy controls. Pooled sensitivity, specificity, and AUC were 0.82 (95% confidence interval [CI] 0.77–0.86), 0.83 (95% CI 0.75–0.89), and 0.88 (95% CI 0.85–0.91), respectively. Abnormal expression of miR-21, miR-26a, miR-192, miR-200c, miR-221, miR-29a, miR-191, miR-181c, miR-34a, miR-106a, miR-203, and miR-373 in patients was confirmed to associate with poor survival rate. Pooled HRs and 95% CIs were calculated using STATA, resulting in the pooled HR of 1.47 (95% CI 0.91–2.37) for overall survival (OS), 0.67 (95% CI 0.16–2.81) for disease-free survival (DFS), 2.31 (95% CI 1.59–3.36) for progression-free survival (PFS), and 2.68 (95% CI 0.88–8.15) for relapse-free survival (RFS). Thus, CCA patients with dysregulated miRNA expression were confirmed to have shorter OS, DFS, PFS, and RFS. Data regarding the diagnostic and prognostic roles of miR-21 suggested pooled diagnostic results of miR-21 for sensitivity, specificity, and AUC were 0.85 (95% CI 0.76–0.91), 0.92 (95% CI 0.81–0.97), and 0.93 (95% CI 0.91–0.95), respectively, suggesting better diagnostic performance of miR-21 compared with other miRNAs. Meanwhile, pooled prognostic result of miR-21 for HR was 1.88 (95% CI 1.41–2.51), indicating miR-21 could more appropriately predict shorter OS in patients with CCA.ConclusionmiRNAs may provide a new approach for clinical application, and miR-21 may be a promising biomarker for diagnosis and prognosis of CCA.

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“…In the case of liver cancer, the global profile of alternative RNA splicing events indicates the existence of differential AS in HCC and iCCA compared to adjacent non-tumor liver tissue, affecting several hundred genes. This information has been proposed as a valuable tool to distinguish different types of liver cancer [ 2 , 38 ].…”

Section: Liver Cancer-associated Alterations In the Spliceosome Machinerymentioning

confidence: 99%

Impact of Alternative Splicing Variants on Liver Cancer Biology

Marin

Reviejo

Soto

et al. 2021

Cancers

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The two most frequent primary cancers affecting the liver, whose incidence is growing worldwide, are hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA), which are among the five most lethal solid tumors with meager 5-year survival rates. The common difficulty in most cases to reach an early diagnosis, the aggressive invasiveness of both tumors, and the lack of favorable response to pharmacotherapy, either classical chemotherapy or modern targeted therapy, account for the poor outcome of these patients. Alternative splicing (AS) during pre-mRNA maturation results in changes that might affect proteins involved in different aspects of cancer biology, such as cell cycle dysregulation, cytoskeleton disorganization, migration, and adhesion, which favors carcinogenesis, tumor promotion, and progression, allowing cancer cells to escape from pharmacological treatments. Reasons accounting for cancer-associated aberrant splicing include mutations that create or disrupt splicing sites or splicing enhancers or silencers, abnormal expression of splicing factors, and impaired signaling pathways affecting the activity of the splicing machinery. Here we have reviewed the available information regarding the impact of AS on liver carcinogenesis and the development of malignant characteristics of HCC and iCCA, whose understanding is required to develop novel therapeutical approaches aimed at manipulating the phenotype of cancer cells.

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Identification of biomarkers of intrahepatic cholangiocarcinoma via integrated analysis of mRNA and miRNA microarray data

Cited by 8 publications

References 36 publications

MicroRNA‑137 suppresses the proliferation, migration and invasion of cholangiocarcinoma cells by targeting WNT2B

MicroRNA‑137 suppresses the proliferation, migration and invasion of cholangiocarcinoma cells by targeting WNT2B

Diagnostic and prognostic value of microRNAs in cholangiocarcinoma: a systematic review and meta-analysis

Impact of Alternative Splicing Variants on Liver Cancer Biology

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