Expression and effect of miR­27b in primary liver cancer.

The occurrence and development of primary liver cancer is associated with microRNA. Specifically, the expression of microRNA-27b (miR-27b) is upregulated in four liver cancer drug-resistance cell lines. Despite that, the function of miR-27b in liver cancer is not clear yet. The aim of the present study was to investigate the effect of miR-27b expression during oncogenesis, cell proliferation, apoptosis and chemotherapy resistance development in a model of liver cancer. Expression of miR-27b was detected with reverse transcription-quantitative PCR. To establish stable overexpression of miR-27b and negative control liver cancer cell lines, a lentiviral pre-miR-27b overexpression vector and negative control vector were transfected into each cell line. Cell Counting Kit-8 assay, clone formation assay and immunohistochemical assay were used to detect cell proliferation. Apoptosis and drug sensitivity were detected by flow cytometry and MTT assay, respectively. The expression level of miR-27b in liver cancer tissues was also lower than in liver tissues adjacent to the tumor. Two stable miR-27b overexpression liver cancer cell lines (Huh-7/miR-27b and HepG2/miR-27b) and their control cell lines (Huh-7/NC and HepG2/NC) were successfully constructed. It was revealed that upregulation of miR-27b can suppress cell proliferation, promote cell apoptosis and chemotherapy resistance. In addition, the findings of the present study demonstrated that patients with cirrhosis expressed lower miR-27b compared with patients without cirrhosis. The expression level of miR-27b was significantly associated with the age, serum alpha-fetoprotein and alanine aminotransferase level of patients with liver cancer. Meanwhile, it was indicated that the disease survival time of the low miR-27b expression group was longer than that of the high miR-27b expression group. The present study suggested that miR-27b functions as a liver cancer suppressor. Moreover, miR-27b can act as a biomarker to estimate drug sensitivity to chemotherapy in patients with liver cancer.

Fusion of NY-ESO-1 epitope with heat shock protein 70 enhances its induced immune responses and antitumor activity against glioma in vitro.

Background: Glioma is the most common tumor originating in the brain and is difficult to cure. New York esophageal squamous cell carcinoma 1 (NY-ESO-1) is a promising cancer testis antigen (CTA) for tumor immunotherapy, and heat shock proteins (HSPs) can promote the antigen presentation of chaperoned peptides. This study investigates the therapeutic potential of HSP70 and NY-ESO-1 epitope fusion protein for glioma. Methods: Recombinant HSP70 protein was purified and fused to NY-ESO-1 epitope to generate HSP70/NY-ESO-1 p86-94. NY-ESO-1 expression was induced in U251 glioma cells via 5-Aza-2'-deoxycytidine (5-Aza-CdR) treatment. Dendritic cells (DCs) loaded with HSP70/NY-ESO-1 p86-94 or NY-ESO-1 protein stimulated NY-ESO-1-specific cytotoxic T lymphocytes (CTLs). The killing effect of NY-ESO-1 specific CTLs on U251 cells was detected by lactate dehydrogenase (LDH). Results: 5-Aza-CdR successfully induced NY-ESO-1 expression in U251 cells. NY-ESO-1-stimulated CTLs lysed more significantly with NY-ESO-1-positive U251 cells than with NY-ESO-1-negative cells. The immune response stimulated by a DC-based vaccine of HSP70/NY-ESO-1 p86-94 fusion protein was significantly enhanced compared with that induced by NY-ESO-1 alone. Conclusions: These findings indicate that the HSP70/NY-ESO-1 p86-94 may significantly enhance CTLs-mediated cytotoxicity and targeting ability against NY-ESO-1-expressing tumors in vitro. 5-Aza-CdR treatment with HSP70 binding to tumor antigen is a new strategy for immunotherapy of the tumors with poor CTA expression.

HDAC2 promotes autophagy-associated HCC malignant progression by transcriptionally activating LAPTM4B.

Hepatocellular carcinoma (HCC) is a significant global health challenge. The activation of autophagy plays an essential role in promoting the proliferation and survival of cancer cells. However, the upstream regulatory network and mechanisms governing autophagy in HCC remain unclear. This study demonstrated that histone deacetylase 2 (HDAC2) regulates autophagy in HCC. Its expression was elevated in HCC tissues, and high HDAC2 expression was strongly associated with poor prognosis in individuals with HCC. Integrated in vitro and in vivo investigations confirmed that HDAC2 promotes autophagy and autophagy-related malignant progression in HCC. Mechanistically, HDAC2 bound specifically to the lysosome-associated protein transmembrane 4-ß (LAPTM4B) promoter at four distinct binding sites, enhancing its transcriptional activation and driving autophagy-related malignant progression in HCC. These findings establish LAPTM4B as a direct target gene of HDAC2. Furthermore, the selective inhibitor of HDAC2 effectively alleviated the malignant development of HCC. In addition, multivariate Cox regression analysis of 105 human HCC samples revealed that HDAC2 expression is an independent predictor of HCC prognosis. This study underscores the crucial role of the HDAC2-LAPTM4B axis in regulating autophagy in the malignant evolution of HCC and highlights the potential of targeting HDAC2 to prevent and halt the malignant progression of HCC.