Wang Shi-Shuo, Huang Zhi-Guang, Wu Hua-Yu, He Rong-Quan, Yang Li-Hua, Feng Zhen-Bo, Dang Yi-Wu, Lu Hui-Ping, Fang Ye-Ying, Chen Gang
Department of Pathology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
Department of Cell Biology & Genetics, Guangxi Medical University, Nanning, Guangxi, China.
PeerJ. 2020 Feb 10;8:e8409. doi: 10.7717/peerj.8409. eCollection 2020.
Hepatocellular carcinoma (HCC) is the second-highest cause of malignancy-related death worldwide, and many physiological and pathological processes, including cancer, are regulated by microRNAs (miRNAs). miR-193a-3p is an anti-oncogene that plays an important part in health and disease biology by interacting with specific targets and signals.
In vitro assays were performed to explore the influences of miR-193a-3p on the propagation and apoptosis of HCC cells. The sequencing data for HCC were obtained from The Cancer Genome Atlas (TCGA), and the expression levels of miR-193a-3p in HCC and non-HCC tissues were calculated. The differential expression of miR-193a-3p in HCC was presented as standardized mean difference (SMD) with 95% confidence intervals (CIs) in Stata SE. The impact of miR-193a-3p on the prognoses of HCC patients was determined by survival analysis. The potential targets of miR-193a-3p were then predicted using miRWalk 2.0 and subjected to enrichment analyses, including Gene Ontology (GO) annotation, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and Protein-Protein Interaction (PPI) network analysis. The interaction between miR-193a-3p and one predicted target, Cyclin D1 (CCND1), was verified by dual luciferase reporter assays and Pearson correlation analysis.
MiR-193a-3p inhibited the propagation and facilitated the apoptosis of HCC cells . The pooled SMD indicated that miR-193a-3p had a low level of expression in HCC (SMD: -0.88, 95% CI [-2.36 -0.59]). Also, HCC patients with a higher level of miR-193a-3p expression tended to have a favorable overall survival (OS: HR = 0.7, 95% CI [0.43-1.13], = 0.14). For the KEGG pathway analysis, the most related pathway was "proteoglycans in cancer", while the most enriched GO term was "protein binding". The dual luciferase reporter assays demonstrated the direct interaction between miR-193a-3p and CCND1, and the Pearson correlation analysis suggested that miR-193a-3p was negatively correlated with CCND1 in HCC tissues ( = - 0.154, = 0.002).
miR-193a-3p could suppress proliferation and promote apoptosis by targeting CCND1 in HCC cells. Further, miR-193a-3p can be used as a promising biomarker for the diagnosis and treatment of HCC in the future.
肝细胞癌（HCC）是全球恶性肿瘤相关死亡的第二大原因，许多生理和病理过程，包括癌症，都受微小RNA（miRNA）调控。miR-193a-3p是一种抑癌基因，通过与特定靶点和信号相互作用，在健康和疾病生物学中发挥重要作用。
进行体外实验以探究miR-193a-3p对HCC细胞增殖和凋亡的影响。从癌症基因组图谱（TCGA）获取HCC的测序数据，并计算miR-193a-3p在HCC组织和非HCC组织中的表达水平。在Stata SE中，将miR-193a-3p在HCC中的差异表达表示为标准化平均差（SMD）及95%置信区间（CI）。通过生存分析确定miR-193a-3p对HCC患者预后的影响。然后使用miRWalk 2.0预测miR-193a-3p的潜在靶点，并进行富集分析，包括基因本体（GO）注释、京都基因与基因组百科全书（KEGG）通路分析和蛋白质-蛋白质相互作用（PPI）网络分析。通过双荧光素酶报告基因实验和Pearson相关性分析验证miR-193a-3p与一个预测靶点细胞周期蛋白D1（CCND1）之间的相互作用。
miR-193a-3p抑制HCC细胞的增殖并促进其凋亡。汇总的SMD表明miR-193a-3p在HCC中表达水平较低（SMD：-0.88，95%CI[-2.36 -0.59]）。此外，miR-193a-3p表达水平较高的HCC患者总体生存率往往较好（OS：HR = 0.7，95%CI[0.43 - 1.13]，P = 0.14）。对于KEGG通路分析，最相关的通路是“癌症中的蛋白聚糖”，而最富集的GO术语是“蛋白质结合”。双荧光素酶报告基因实验证明了miR-193a-3p与CCND1之间的直接相互作用，Pearson相关性分析表明miR-193a-3p与HCC组织中的CCND1呈负相关（r = - 0.154，P = 0.002）。
miR-193a-3p可通过靶向HCC细胞中的CCND1抑制增殖并促进凋亡。此外，miR-193a-3p未来有望作为HCC诊断和治疗的生物标志物。
