A comprehensive insight into the clinicopathologic significance of miR-144-3p in hepatocellular carcinoma

Abstract

BackgroundStudies which focused on the character of miR-144-3p in hepatocellular carcinoma (HCC) are limited. This study aimed to explore the expression, clinical significance and the potential targets of miR-144-3p in HCC.MethodsThe Cancer Genome Atlas (TCGA) and a cohort of 95 cases of HCC were applied to investigate aberrant miR-144-3p expression in HCC. A meta-analysis was performed to accumulate data on miR-144-3p expression in HCC based on TCGA, quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Gene Expression Omnibus (GEO). Additionally, the potential regulatory mechanisms of miR-144-3p in HCC were explored by bioinformatics.ResultsMiR-144-3p expression was downregulated distinctly in HCC compared to para-HCC tissue both in TCGA data (8.9139±1.5986 vs 10.7721±0.9156, P<0.001) and in our qRT-PCR validation (1.3208±0.7594 vs 2.6200±0.9263, P<0.001). The meta-analysis based on TCGA, qRT-PCR and GEO data confirmed a consistent result (standard mean difference =−0.854, 95% CI: −1.224 to −0.484, P<0.001). The receiver operating characteristic curve of miR-144-3p gained a significant diagnostic value both in TCGA data (area under the curve [AUC] =0.852, 95% CI: 0.810 to 0.894, P<0.001) and in qRT-PCR validation (AUC =0.867, 95% CI: 0.817 to 0.916, P<0.001), especially in alpha-fetoprotein–negative HCC patients (AUC =0.900, 95% CI: 0.839 to 0.960, P<0.001). Furthermore, we identified 119 potential targets of miR-144-3p in HCC by bioinformatics. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses revealed that several significant biologic functions and pathways correlated with the pathogenesis of HCC, including the p53 signaling pathway.ConclusionMiR-144-3p may function as a cancer suppressor microRNA, which is essential for HCC progression through the regulation of various signaling pathways. Thus, interactions with miR-144-3p may provide a novel treatment strategy for HCC in the future.

Effects of miR-144 on the sensitivity of human anaplastic thyroid carcinoma cells to cisplatin by autophagy regulation

“…Acting as either oncogenes or tumor suppressors during tumorigenesis, they can play a causal role in the occurrence, development and progression of cancers. 10 MiR-144 has been identified as a tumor suppressor in a spectrum of human cancers such as lung cancer, nasopharyngeal carcinoma, hepatocellular carcinoma and clear cell renal cell carcinoma etc.. [11][12][13][14][15][16][17][18][19] In addition, miR-144 has been most thoroughly studied in hepatocellular carcinoma according to our research. However, very few studies focusing on the role of miR-144 in thyroid carcinoma were published.…”

miR-144-5p Enhances the Radiosensitivity of Non-Small-Cell Lung Cancer Cells via Targeting ATF2

“…During miRNA biogenesis, only the guide strand is processed to bind to the RNA-induced silencing complex to target mRNAs, whereas the passenger strand is degraded [ 6 , 22 ]. It is well documented that miR-144-3p is downregulated and serves as a tumor suppressor in a variety of tumors, including lung cancer [ 23 ], gastric cancer [ 24 ], breast cancer [ 25 ], pancreatic cancer [ 26 ], and hepatocellular carcinoma [ 27 ]. Nevertheless, the function of miR-144-5p, the guide strand from pre-miR-144, is largely unknown.…”

miR-144-3p inhibits cell proliferation of colorectal cancer cells by targeting BCL6 via inhibition of Wnt/β-catenin signaling

“…miR-144-3p exerts the effect of a tumor suppressor on glioblastoma through regulating c-Met [8]. Moreover, in hepatocellular carcinoma (HCC), miR-144-3p acts as a tumor suppressor microRNA to regulate the progression of HCC [9,10]. In pancreatic cancer, MiR-144-3p inhibits cell proliferation, migration, and invasion through targeting AP-1 transcription factor subunit (FOSB) and promotes cell apoptosis and cell cycle arrest by targeting proline-rich protein 11 [11,12].…”