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Objective To explore the expression, clinical significance and molecular mechanism of miR-3934-5p in hepatocellular carcinoma (HCC). Methods HCC tissues and adjacent normal tissues were collected from 53 HCC patients diagnosed in our hospital from September 2013 to August 2014. Real-time quantitative PCR (RT-qPCR) was performed to detect the level of miR-3934-5p in the above tissues and human liver cell line L02 and HCC cell lines. The Cancer Genome Atlas (TCGA) database was used to analyze the expression of miR-3934-5p in normal liver tissues and HCC tissues; Chi-square test with Kaplan-Meier survival curve were applied to analyze the correlation of miR-3934-5p and clinicopathological characteristics and survival prognosis; RT-qPCR and Western blotting were adopted to detect transfection efficiency; CCK-8 assay, colony formation assay and EdU assay were employed respectively to evaluate the activity and proliferation of HCCLM3 cells; Spearman correlation analysis was applied to study the correlation between LACTB mRNA and miR-3934-5p expression in HCC tissues; TargetScan database was used to predict the downstream target genes of miR-3934-5p, and the prediction results was verified by luciferase reporter assay. Results MiR-3934-5p was highly expressed in the liver cancer tissues and cells (P < 0.05), and its high expression was significantly correlated with tumor size (P=0.040), tumor multiplicity (P=0.013), vascular invasion (P=0.006), and TNM stage (P=0.017); Compared to the low miR-3934-5p expression group, the HCC patients with high expression had poorer survival prognosis. CCK-8 assay, colony formation assay and EdU assay confirmed that knocking down miR-3934-5p notably inhibited the proliferation of HCCLM3 cells (P < 0.05). LACTB had been proved to be the direct target of miR-3934-5p, and mediated the biological effect of miR-3934-5p on HCC cells. Conclusion MiR-3934-5p promotes the proliferation of HCC cells by targeting tumor suppressor gene LACTB.

The bromodomain protein zinc finger MYND-type containing 8 (ZMYND8) plays a critical role in human breast cancer. However, the expression and biological function of ZMYND8 in hepatocellular carcinoma (HCC) are poorly understood. In this study, ZMYND8 expression was found to be elevated in HCC based on the cancer genome atlas (TCGA) and gene expression omnibus (GEO) databases. Next, we confirmed that ZMYND8 was frequently overexpressed in HCC tissues compared with adjacent non-tumor tissues. The up-regulated level of ZMYND8 was also observed in HCC cell lines. Elevated ZMYND8 expression was correlated with unfavorable clinicopathological features and poor prognosis of HCC patients. Functionally, ectopic expression of ZMYND8 potentiated the proliferation, migration, and invasion of Hep3B cells. Conversely, ZMYND8 knockdown led to the reduced proliferation and invasiveness of HCCLM3 cells. ZMYND8 silencing restrained the growth of HCCLM3 cells in vivo. Mechanistically, ZMYND8 enhanced glucose consumption, lactate production, and ATP level in HCC cells. Pharmacological inhibition of glycolysis using 2-DG blocked the promoting effects of ZMYND8 on HCC cell proliferation and mobility. Furthermore, hexokinase 2 (HK2), a key enzyme of glycolysis, was identified as the downstream target of ZMYND8 in HCC cells. ZMYND8 promoted HK2 transcription by recruiting bromodomain containing 4 (BRD4) to its promoter. Knockdown of HK2 abrogated the oncogenic functions of ZMYND8 in HCC. Altogether, these data indicated that ZMYND8 promoted the growth and metastasis of HCC by promoting HK2-mediated glycolysis and might serve as a promising biomarker and therapeutic target for HCC., (Copyright © 2021 Elsevier GmbH. All rights reserved.)

Hepatocellular carcinoma (HCC) is the most predominant type of primary liver cancer and has a high degree of malignancy as well as mortality rate. Many drivers are involved in the development and progression of HCC. A recent study has reported that high BICD cargo adaptor 1 (BICD1) expression indicates poor prognosis of glioblastoma. But, the expression and biological function of BICD1 in HCC remain unclear. In current study, we found that the expression of BICD1 was markedly up-regulated in HCC tissues compared to adjacent nontumor tissues. GEPIA dataset and GSE datasets were consistently indicated the elevated expression of BICD1 in HCC. Furthermore, BICD1 was highly expressed in HCC cell lines including Hep3B, Huh7, MHCC97H and HCCLM3 as compared with that in LO2 cells. High BICD1 expression was positively correlated with malignant clinical features, such as tumor size ≥ 5 cm, venous infiltration and advanced tumor stages. HCC patients highly expressing BICD1 showed a significant shorter overall survival compared to BICD1 low-expression cases. Moreover, TCGA-LIHC data further demonstrated that the up-regulated BICD1 expression predicted poor prognosis of HCC patients. Next, we revealed that BICD1 knockdown prominently suppressed the proliferation, migration and invasion of HCCLM3 cells. Conversely, ectopic expression of BICD1 remarkably facilitated these malignant behaviors of Hep3B cells. Interestingly, BICD1 knockdown abolished hypoxia-induced HCC cell proliferation, migration and invasion. In conclusion, we provide the first evidence to support that BICD1 functions as a predictor for the prognosis of HCC and may serve as a promising therapeutic target for further HCC treatment., Competing Interests: Declaration of Competing Interest All authors declare no conflicts of interest., (Copyright © 2020 Elsevier GmbH. All rights reserved.)