The aim of the present study was to elucidate whether, and how, long intergenic non-protein coding RNA 1296 (LINC01296) is involved in the modulation of human cholangiocarcinoma (CCA) development and progression. Microarray data analysis and reverse transcription-quantitative polymerase chain reaction analysis demonstrated that LINC01296 was significantly upregulated in human CCA compared with nontumor tissues. Furthermore, the expression of LINC01296 in human CCA was positively associated with tumor severity and clinical stage. Knockdown of LINC01296 dramatically suppressed the viability, migration and invasion of RBE and CCLP1 cells, and promoted cell apoptosis in vitro. Furthermore, LINC01296 knockdown inhibited tumor growth in a xenograft model. Mechanistically, LINC01296 was demonstrated to sponge microRNA-5095 (miR-5095), which targets MYCN proto-oncogene bHLH transcription factor (MYCN) mRNA in human CCA. By inhibition of miR-5095, LINC01296 overexpression upregulated the expression of MYCN and promoted cell viability, migration and invasion in CCA cells. The results reveal that the axis of LINC01296/miR-5095/MYCN may be a mechanism to regulate CCA development and progression.

Expression of TGF-β1 and miR-99a in patients with early spontaneous abortion and correlation with hormone levels during pregnancy were investigated. A total of 70 pregnant women with early spontaneous abortion diagnosed in Jining No. 1 People's Hospital from February 1, 2015 to May 1, 2018 were selected as the study group, and 83 normal pregnant women who chose abortion for non-medical reasons in the same period as the control group. Enzyme-linked immunosorbent assay (ELISA) was used to detect TGF-β1 and the levels of serum β-HCG, progesterone and estrogen during pregnancy in the two groups, and RT-qPCR to detect the expression of miR-99a, and partial correlation analysis to analyze the correlation of TGF-β1 and miR-99a with the levels of serum β-HCG, progesterone and estrogen in the study group of patients. Expression of β-HCG was significantly lower in the study group than that in the control group, with a statistically significant difference (P<0.001), and that of progesterone was significantly lower in the study group than that in the control group, with a statistically significant difference (P<0.001). Expression of estrogen was significantly lower in the study group than that in the control group, with a statistically significant difference (P<0.001). The partial correlation analysis indicated that the levels of serum β-HCG, progesterone and estrogen were positively correlated with TGF-β1 (r=0.944, 0.868, 0.869, P<0.001), negatively correlated with the expression level of miR-99a (r=−0.944, −0.892, −0.891, all P<0.001). miR-99a was highly expressed in the serum of patients with early spontaneous abortion, but TGF-β1 expression was low. The expression levels of the two factors are related to hormone levels during pregnancy, which are expected to be new candidate molecular diagnostic markers in the diagnosis of early spontaneous abortion.

Hepato-pancreato-biliary (HPB) cancer is a serious category of cancer including tumors originating in the liver, pancreas, gallbladder and biliary ducts. It is limited by two-dimensional (2D) cell culture models for studying its complicated tumor microenvironment including diverse contents and dynamic nature. Recently developed three-dimensional (3D) bioprinting is a state-of-the-art technology for fabrication of biological constructs through layer-by-layer deposition of bioinks in a spatially defined manner, which is computer-aided and designed to generate viable 3D constructs. 3D bioprinting has the potential to more closely recapitulate the tumor microenvironment, dynamic and complex cell-cell and cell-matrix interactions compared to the current methods, which benefits from its precise definition of positioning of various cell types and perfusing network in a high-throughput manner. In this review, we introduce and compare multiple types of 3D bioprinting methodologies for HPB cancer and other digestive tumors. We discuss the progress and application of 3D bioprinting in HPB and gastrointestinal cancers, focusing on tumor model manufacturing. We also highlight the current challenges regarding clinical translation of 3D bioprinting and bioinks in the field of digestive tumor research. Finally, we suggest valuable perspectives for this advanced technology, including combination of 3D bioprinting with microfluidics and application of 3D bioprinting in the field of tumor immunology.