ABSTRACT
Hexokinase 2 (HK2) has been associated with carcinogenic growth in numerous kinds of malignancies as essential regulators during the processing of glucose. This study aimed to explore the effects of HK2 on diffuse large B-cell lymphoma (DLBCL) cells via the ERK1/2 signaling. Expressions of HK2 and ERK1/2 were examined in DLBCL cell lines using quantitative reverse transcription polymerase chain reaction and western blotting. HK2 and ERK1/2 were attenuated through HK2 small-interfering RNA (siRNA) and ERK inhibitor FR180204, respectively, in U2932 and SU-DHL-4 cells. Cell Counting Kit-8, clone formation, transwell, and flow cytometry assays were used in evaluating the effects of HK2 and ERK1/2 on cell proliferation, migration, and apoptosis. Moreover, a xenograft model was created to assess the roles of HK2 in vivo. HK2 and ERK1/2 were evidently up-regulated in DLBCL cell lines. HK2 knockdown and FR180204 markedly suppressed the proliferation and clonogenesis of U2932 and SU-DHL-4 cells and promoted cell apoptosis in vitro. We also found that HK2 silencing suppressed tumor growth in vivo. Notably, HK2 knockdown inactivated the ERK1/2 signaling pathway both in vitro and in vivo. These data indicate that inhibition of HK2 may suppress the proliferation, migration, and invasion of DLBCL cells, partly via inhibiting the ERK1/2 signaling pathway.
ABSTRACT
BACKGROUND: To glean insights into the relationship among hepatitis B virus (HBV) genotype/subgenotypes, A1762T/G1764A mutations and advanced liver disease such as liver cirrhosis (LC) and hepatocellular carcinoma (HCC) in Southeast China. METHODS: A case-control study was performed, consisting of chronic hepatitis B (CHB) patients (n=160), LC patients (n=150), and HCC patients (n=156). Fluorescence quantitative polymerase chain reaction (FQ-PCR) was used to detect A1762T/G1764A mutations. HBV genotypes/subgenotypes were determined by multiplex PCR. All patients' clinical data was systematically collected from the hospital records. RESULTS: Our study revealed HBV genotypes C (63.95%) and B (33.69%) were predominant in chronically infected patients, subgenotype B2, C2 and C1 were the major subgenotypes. Both subgenotype C2 infection and A1762T/G1764A mutations were associated with LC and HCC with cirrhosis, subgenotype C2 (OR=2.033, 95%CI=1.246-3.323, P=0.003 for LC vs CHB; OR=3.247, 95%CI=1.742-6.096, P=0.001 for HCC with cirrhosis vs CHB; respectively ), and A1762T/G1764A mutations (OR=1.914, 95%CI=1.188-3.085, P=0.005 for LC vs CHB; OR=2.996, 95%CI=1.683-5.353, P=0.002 for HCC with cirrhosis vs CHB; respectively), but no differences in the frequencies of both variants between LC and HCC with cirrhosis groups were found. CONCLUSIONS: HBV subgenotype C2 infection and A1762T/G1764A mutations are both risk factors of LC and HCC with cirrhosis development in the patients with CHB in Southeast China, but all no helpful for predicting HCC development in LC patients.
