Background Hepatocellular carcinoma (HCC) is the most common malignant liver tumor with poor clinical outcomes. Increasing amount of long non-coding RNAs (lncRNAs) have been revealed to be implicated in the carcinogenesis and progression of HCC. However, the expressions, clinical significances, and roles of most lncRNAs in HCC are still unknown. Methods The expression of lncRNA MCM3AP antisense RNA 1 (MCM3AP-AS1) in HCC tissues and cell lines was detected by qRT-PCR and fluorescence in situ hybridization. Immunoblotting, CCK-8, EdU, colony formation and flow cytometry were performed to investigate the role of MCM3AP-AS1 in HCC cell proliferation, cell cycle and apoptosis in vitro. A subcutaneous tumor mouse model was constructed to analyze in vivo growth of HCC cells after MCM3AP-AS1 knockdown. The interactions among MCM3AP-AS1, miR-194-5p and FOXA1 were measured by RNA pull-down, RNA immunoprecipitation and luciferase reporter assay. Results We revealed a novel oncogenic lncRNA MCM3AP-AS1, which is overexpressed in HCC and positively correlated with large tumor size, high tumor grade, advanced tumor stage and poor prognosis of HCC patients. MCM3AP-AS1 knockdown suppressed HCC cell proliferation, colony formation and cell cycle progression, and induced apoptosis in vitro, and depletion of MCM3AP-AS1 inhibited tumor growth of HCC in vivo. Mechanistically, MCM3AP-AS1 directly bound to miR-194-5p and acted as competing endogenous RNA (ceRNA), and subsequently facilitated miR-194-5p’s target gene forkhead box A1 (FOXA1) expression in HCC cells. Interestingly, FOXA1 restoration rescued MCM3AP-AS1 knockdown induced proliferation inhibition, G1 arrest and apoptosis of HCC cells. Conclusions Our results recognized MCM3AP-AS1 as a novel oncogenic lncRNA, which indicated poor clinical outcomes in patients with HCC. MCM3AP-AS1 exerted an oncogenic role in HCC via targeting miR-194-5p and subsequently promoted FOXA1 expression. Our findings suggested that MCM3AP-AS1 could be a potential prognostic biomarker and therapeutic target for HCC. Electronic supplementary material The online version of this article (10.1186/s12943-019-0957-7) contains supplementary material, which is available to authorized users.

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Maintenance of an appropriate oxygen concentration is essential for the function of the liver. However, in many pathological conditions, and particularly in the tumor microenvironment, cells and tissues are frequently in a hypoxic state. In the presence of hypoxia, the cells adapt to the low oxygen levels through the hypoxia-inducible factor (HIF) pathway. Overgrowth of tumor cells restricts the diffusion of oxygen in tumors, leading to insufficient blood supply and the creation of a hypoxic microenvironment, and, as a consequence, activation of the expression of HIFs. HIFs possess a wide range of target genes, which function to control a variety of signaling pathways; thus, HIFs modulate cellular metabolism, immune escape, angiogenesis, metastasis, extracellular matrix remodeling, cancer stem cells and other properties of the tumor. Given their crucial role in the occurrence and development of tumors, HIFs are expected to become new targets of precise treatment of hepatocellular carcinoma.

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The aberrant expression and dysfunction of long non‐coding RNAs (lncRNAs) have been identified as critical factors governing the initiation and progression of different human cancers, including diffuse large B‐cell lymphoma (DLBCL). LncRNA small nucleolar RNA host gene 16 (SNHG16) has been recognized as a tumour‐promoting factor in various types of cancer. However, the biological role of SNHG16 and its underlying mechanism are still unknown in DLBCL. Here we disclosed that SNHG16 was overexpressed in DLBCL tissues and the derived cell lines. SNHG16 knockdown significantly suppressed cell proliferation and cell cycle progression, and it induced apoptosis of DLBCL cells in vitro. Furthermore, silencing of SNHG16 markedly repressed in vivo growth of OCI‐LY7 cells. Mechanistically, SNHG16 directly interacted with miR‐497‐5p by acting as a competing endogenous RNA (ceRNA) and inversely regulated the abundance of miR‐497‐5p in DLBCL cells. Moreover, the proto‐oncogene proviral integration site for Moloney murine leukaemia virus 1 (PIM1) was identified as a novel direct target of miR‐497‐5p. SNHG16 overexpression rescued miR‐497‐5p‐induced down‐regulation of PIM1 in DLBCL cells. Importantly, restoration of PIM1 expression reversed SNHG16 knockdown‐induced inhibition of proliferation, G0/G1 phase arrest and apoptosis of OCI‐LY7 cells. Our study suggests that the SNHG16/miR‐497‐5p/PIM1 axis may provide promising therapeutic targets for DLBCL progression.

TGFβ2 is an essential regulator of immune cell functionality, but the mechanisms whereby it drives immune infiltration in gastric cancer remain uncertain. The Oncomine and Tumor Immunoassay Resource (TIMER) databases were used for assessing the expression of TGFβ2, after which TIMER was used to explore the relationship between TGFβ2 and tumour immune infiltration. Finally, we assessed how TGFβ2 expression correlated with the expression of a set of marker genes associated with immune infiltration using TIMER and GEPIA. We determined TGFβ2 expression to be significantly correlated with outcome in multiple types of cancer in the Cancer Genome Atlas (TCGA), with the effect being particularly pronounced in gastric cancer. Furthermore, elevated TGFβ2 expression was found to be significantly correlated with gastric cancer N staging, and with the expression of a variety of immune markers associated with particular immune cell subsets. These results indicate that TGFΒ2 is associated with patient outcome and tumour immune cell infiltration in multiple cancer types. This suggests that TGFβ2 is a key factor which governs immune cell recruitment to gastric cancer tumours, potentially playing a vital role in governing immune cell infiltration and thus representing a valuable prognostic biomarker in gastric cancer patients.

Background/Aims: Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm. Tyrosine kinase inhibitors (TKIs) are commonly used to treat CML; however, drug resistance of CML cells to TKIs has limited their clinical application. Shikonin, a traditional Chinese herb, has long been used to treat leukemia in China, but the roles and related molecular mechanisms of shikonin treatment in CML remain unclear. Here, we aimed to evaluate the effects of shikonin on the proliferation, apoptosis, and migration of K562 cells, a CML cell line. Methods: Firstly, K562 cell proliferation and apoptosis were tested by CCK8 assay and flow cytometry with Annexin V-FITC/PI staining. Cell migration was measured by Transwell migration assay. In addition, western blot was performed to determine the proteins (PI3K, Bax, Bcl-2, cleaved caspase-3, PTEN, p-AKT, AKT, CXCR4, SDF-1, CD44) involved in the mechanism of action of shikonin. Finally, neutrophils from peripheral blood of CML patients were obtained, and cell proliferation and apoptosis were tested by CCK8 assay and flow cytometry. Results: Shikonin reduced the proliferation of K562 cells in a time- and dose-dependent manner and promoted the apoptosis of K562 cells. Moreover, shikonin increased the PTEN level and inactivated the PI3K/AKT signaling pathway, subsequently upregulating BAX in K562 cells. In addition, shikonin could block K562 cell migration via the CXCR4/SDF-1 axis. Finally, shikonin significantly inhibited the proliferation and promoted the apoptosis of neutrophils from CML patients. Conclusion: These results demonstrated that shikonin inhibits CML proliferation and migration and induces apoptosis by the PTEN/PI3K/AKT pathway, revealing the effects of shikonin therapy on CML.