Hepatocellular carcinoma (HCC) represents a malignant tumor predominantly arising in the setting of cirrhosis and is the third most common cause of cancer-associated death on a global scale. The heterogeneous nature of HCC and limited well-recognized biomarkers may contribute to poor patient prognosis and treatment failure. In this study, we identified expression pattern of microRNA-202-3p (miR-202-3p) in HCC and characterized its functional role as well as related mechanisms. First, we collected 50 HCC tissues and 38 normal liver tissues, and after bioinformatics prediction, the expression of miR-202-3p and KDM3A was determined in the tissues. We found lowly expressed miR-202-3p and overexpressed KDM3A in HCC tissues. Then, dual-luciferase reporter gene assay was employed to test the presence of miR-202-3p binding sites in the 3’UTR of KDM3A and chromatin immunoprecipitation (ChIP) assay to homeobox A1 (HOXA1) interaction with KDM3A and MEIS3. It has been confirmed that miR-202-3p negatively regulated KDM3A responsible for increasing the expression of HOXA1 by eliminating the histone H3 lysine 9 (H3K9)me2 in HCC cells. HOXA1 could evidently increase H3K4me1 and H3K27ac enrichment in the MEIS3 enhancer region and enhance the expression of MEIS3. Functional assays were also performed with the results showing that upregulated miR-202-3p or downregulated KDM3A retarded HCC cell viability, migration, and invasion. In addition, HepG2 cells were xenografted into nude mice, and we demonstrated that upregulated miR-202-3p reduced the growth of human HCC cells in vivo. Taken together, the present study elicits a novel miR-202-3p/KDM3A/HOXA1/MEIS3 pathway in HCC, potentiating an exquisite therapeutic target for HCC.

肝细胞癌（HCC）代表主要在肝硬化背景下发生的恶性肿瘤，是全球范围内与癌症相关的死亡的第三大最常见原因。HCC的异质性和有限的公认的生物标志物可能导致患者预后不良和治疗失败。在这项研究中，我们确定了microRNA-202-3p（miR-202-3p）在肝癌中的表达模式，并表征了其功能作用和相关机制。首先，我们收集了50例HCC组织和38例正常肝组织，并经过生物信息学预测，确定了组织中miR-202-3p和KDM3A的表达。我们发现在肝癌组织中低表达的miR-202-3p和过表达的KDM3A。然后，采用双荧光素酶报告基因检测在KDM3A的3'UTR中是否存在miR-202-3p结合位点，以及染色质免疫沉淀（ChIP）检测同源盒A1（HOXA1）与KDM3A和MEIS3的相互作用。已经证实，miR-202-3p通过消除HCC细胞中的组蛋白H3赖氨酸9（H3K9）me2负调控KDM3A，从而增加HOXA1的表达。HOXA1可以明显增加H3K4me1和H3K27ac在MEIS3增强子区域的富集并增强MEIS3的表达。还进行功能测定，结果表明miR-202-3p上调或KDM3A下调可抑制HCC细胞活力，迁移和侵袭。此外，将HepG2细胞异种移植到裸鼠中，我们证明了miR-202-3p上调会降低人HCC细胞的生长 已经证实，miR-202-3p通过消除HCC细胞中的组蛋白H3赖氨酸9（H3K9）me2而负调控KDM3A的表达，从而增加HOXA1的表达。HOXA1可以明显增加H3K4me1和H3K27ac在MEIS3增强子区域的富集并增强MEIS3的表达。还进行功能测定，结果表明miR-202-3p上调或KDM3A下调可抑制HCC细胞活力，迁移和侵袭。此外，将HepG2细胞异种移植到裸鼠中，我们证明了miR-202-3p上调会降低人HCC细胞的生长 已经证实，miR-202-3p通过消除HCC细胞中的组蛋白H3赖氨酸9（H3K9）me2负调控KDM3A，从而增加HOXA1的表达。HOXA1可以明显增加H3K4me1和H3K27ac在MEIS3增强子区域的富集并增强MEIS3的表达。还进行功能测定，结果表明miR-202-3p上调或KDM3A下调可抑制HCC细胞活力，迁移和侵袭。此外，将HepG2细胞异种移植到裸鼠中，我们证明了miR-202-3p上调会降低人HCC细胞的生长 HOXA1可以明显增加H3K4me1和H3K27ac在MEIS3增强子区域的富集并增强MEIS3的表达。还进行功能测定，结果表明miR-202-3p上调或KDM3A下调可抑制HCC细胞活力，迁移和侵袭。此外，将HepG2细胞异种移植到裸鼠中，我们证明了miR-202-3p上调会降低人HCC细胞的生长 HOXA1可以明显增加H3K4me1和H3K27ac在MEIS3增强子区域的富集并增强MEIS3的表达。还进行功能测定，结果表明miR-202-3p上调或KDM3A下调可抑制HCC细胞活力，迁移和侵袭。此外，将HepG2细胞异种移植到裸鼠中，我们证明了miR-202-3p上调会降低人HCC细胞的生长体内。综上所述，本研究在HCC中引发了一条新的miR-202-3p / KDM3A / HOXA1 / MEIS3途径，从而为HCC提供了一个精致的治疗靶点。