Dataset Information

MicroRNA-497-5p Is Downregulated in Hepatocellular Carcinoma and Associated with Tumorigenesis and Poor Prognosis in Patients.

ABSTRACT:

Background

MicroRNAs (miRNAs) have been demonstrated to exhibit important regulatory roles in multiple malignancies, including hepatocellular carcinoma (HCC). hsa-miR-497-5p was reported to involve in cancer progression and poor prognosis in many kinds of tumors. However, the expression and its clinical significance of hsa-miR-497-5p in HCC remain unclear.

Methods

In the present study, we investigated the expression of hsa-miR-497-5p in HCC and analyzed the correction of clinical features with prognosis. The expression levels of hsa-miR-497-5p and potential target genes were analyzed in HCC and adjacent noncancerous tissues using The Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) datasets. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to analyze hsa-miR-497-5p levels in 328 HCC tissues and 30 paired adjacent noncancer tissues. Overall survival (OS) and progression-free survival (PFS) of patients with HCC were assessed using the Kaplan-Meier method and the log-rank test.

Results

The hsa-miR-497-5p expression levels were decreased, and its target genes ACTG1, CSNK1D, PPP1CC, and BIRC5 were upregulated in HCC tissues compared with normal tissues. Lower levels of hsa-miR-497-5p expression and higher levels of the four target genes were significantly associated with higher tumor diameter. Moreover, patients with lower hsa-miR-497-5p expression and higher target genes levels had shorter OS.

Conclusion

The expression levels of hsa-miR-497-5p may play an important regulatory role in HCC and are closely correlated with HCC progression and poor prognosis in patients. The hsa-miR-497-5p may be a specific therapeutic target for the treatment of HCC.

SUBMITTER: Tian LL

PROVIDER: S-EPMC7987441 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Hepatocellular carcinoma (HCC) is generally considered one of the most common gastrointestinal malignant tumors, characterized by high invasiveness and metastatic rate, as well as insidious onset. A relationship between carcinogenicity and aberrant microRNA-139-5p (miR-139-5p) expression has been identified in multiple tumors while the specific molecular mechanisms of miR-139-5p in HCC have not yet been thoroughly elucidated. A meta-analysis of available data from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus, ArrayExpress and Oncomine databases, as well as the published literature, was comprehensively conducted with the aim of examining the impact of miR-139-5p expression on HCC. Additionally, predicted downstream target genes were confirmed using a series of bioinformatics tools. Moreover, a correlative biological analysis was performed to ascertain the precise function of miR-139-5p in HCC. The results revealed that the expression of miR-139-5p was noticeably lower in HCC compared with non-tumor liver tissues according to the pooled standard mean difference, which was -0.84 [95% confidence interval (CI): -1.36 to -0.32; P<0.001]. Furthermore, associations were detected between miR-139-5p expression and certain clinicopathological characteristics of TCGA samples, including tumor grade, pathological stage and T stage. Moreover, the pooled hazard ratio (HR) for overall survival (HR=1.37; 95% CI: 1.07-1.76; P=0.001) indicated that decreased miR-139-5p expression was a risk factor for adverse outcomes. Additionally, 382 intersecting genes regulated by miR-139-5p were obtained and assembled in signaling pathways, including 'transcription factor activity, sequence-specific DNA binding', 'pathways in cancer' and 'Ras signaling pathway'. Notably, four targeted genes that were focused in 'pathways in cancer' were identified as hub genes and immunohistochemical staining of the proteins encoded by these four hub genes in liver tissues, explored using the Human Protein Atlas database, confirmed their expression patterns in HCC and normal liver tissues Findings of the present study suggest that reduced miR-139-5p expression is capable of accelerating tumor progression and is associated with a poor clinical outcome by modulating the expression of downstream target genes involved in tumor-associated signaling pathways.