MicroRNAs (miRNAs) are important regulators of multiple cellular processes, and the deregulation of miRNA is a common event in diverse human diseases, particularly cancer. However, the mechanisms underlying the relationship between disordered miRNA expression and tumorigenesis have remained largely unknown. In this study, we demonstrated the down-regulation of miR-125b in hepatocellular carcinoma (HCC) tissues and HCC cell lines by Northern blot and quantitative RT-PCR analyses. The ectopic expression of miR-125b reduced the cellular proliferation and cell cycle progression of HCC cells by targeting Mcl-1 and IL6R. Furthermore, the miR-125b-induced inhibition of cell proliferation was rescued by the expression of Mcl-1 or IL6R variants that lacked 3' UTRs. Thus, this study revealed the differential expression of miR-125b in HCC cells and elucidated its potential as a tumor suppressor in HCC development.

Colorectal cancer (CRC) is one of the malignant tumors with the highest morbidity and mortality and poor prognosis. The mammalian gene family of Cab45/reticulocalbin/ERC-45/calumenin (CREC) consists of RCN1, RCN2, RCN3, SDF4 and CALU. Although CREC family members have been associated with CRC, the expression pattern, prognostic value, and the role of CREC family in CRC remain unclear. In this study, the expression, survival and biological functions of CREC family in CRC were determined via bioinformatic datasets analysis and experimental verification on clinical CRC specimen. Bioinformatic analysis showed that the expression levels of most CREC family genes were higher in CRC tissues than in normal colorectal tissues. The qPCR and western blot results also revealed that the transcriptional and protein levels of CREC family were elevated in CRC tissues compared with adjacent tissues. Besides, CREC family was significantly correlated with advanced tumor stage and poor prognosis of CRC patients. The expression levels of CREC family had correlations with genomic mutation and methylation, and with the infiltration levels of CD4 + T cells, macrophages, neutrophils, and dendritic cells in the microenvironment of CRC. Functional networks enrichment analysis indicated that the genes of CREC family were essential factors for CRC metastasis. Collectively, these findings suggest that CREC family might be potential targets for the treatment of CRC and candidate prognostic markers for CRC patients.

Mounting evidences have indicated that RNA N⁶-methyladenosine (m⁶A) modification played important roles in tumor formation and growth. However, it is rarely reported that m⁶A modifications are involved in the immune regulation and tumor microenvironment (TME) formation. In this study, we aimed to investigate the correlation between m⁶A modifications and TME regulation of colon adenocarcinoma (COAD) by bioinformatic analysis. NMF algorithm was applied to carry out consensus molecular subtype analysis on 36 selected m⁶A regulators regarding methylation modification, to identify m⁶A modification patterns and characteristics of m⁶A related genes in colon adenocarcinoma (COAD). Further, the relative infiltration levels of different immune cell subsets were quantified by ssGSEA and CIBERSORT algorithms, and a m⁶Sig scoring scheme was constructed to predict the prognosis and evaluate the response to immunotherapy in the patients with COAD. Among 579 COAD samples, we identified three different m⁶A modification patterns which were related to different biological pathways and clinical outcomes. Then, a scoring scheme termed "m⁶Sig score" was developed based on m⁶A-related characteristic genes, and was utilized to score patients with COAD into groups. We found that COAD patients with lower m⁶Sig scores exhibited prolonged survival and potentiated immune infiltration, which were associated with higher tumor mutation load, lower PD-L1 expression, and higher mutation rates of SMG (such as TTN and KRAS). Moreover, analysis regarding evaluation of immune response revealed that the patients with lower m⁶Sig scores had higher Immunophenoscore. Collectively, our study provided in depth insight into the interactions between m⁶A modification and regulation of TME. In addition, the quantitative evaluation of m⁶A modification patterns in our results may have implications in further immunotherapy for individual COAD patients.

Often, alternative splicing is used by cancer cells to produce or increase proteins that promote growth and survival through alternative splicing. Although RNA-binding proteins are known to regulate alternative splicing events associated with tumorigenesis, their role in oesophageal cancer (EC) has rarely been explored. We analysed the expression pattern of several relatively well characterized splicing regulators on 183 samples from TCGA cohort of oesophageal cancer; the effectiveness of the knockdown of SRSF2 was subsequently verified by immunoblotting; we measured the ability of cells treated with lenti-sh-SRSF2/lenti-sh2-SRSF2 to invade through an extracellular matrix coating by transwell invasion assay; using RNA-seq data to identify its potential target genes; we performed qRT-PCR to detect the changes of exon 2 usage in lenti-sh-SRSF2 transduced KYSE30 cells to determine the possible effect of SRSF2 on splicing regulation of IRF3; RNA Electrophoretic mobility shift assay (RNA-EMSA) was performed by the incubation of purified SRSF2 protein and biotinylated RNA probes; we performed luciferase assay to confirm the effect of SRSF2 on IFN1 promoter activity. We found upregulation of SRSF2 is correlated with the development of EC; Knock-down of SRSF2 inhibits EC cell proliferation, migration, and invasion; SRSF2 regulates the splicing pattern of IRF3 in EC cells; SRSF2 interacts with exon 2 of IRF3 to regulate its exclusion; SRSF2 inhibits the transcription of IFN1 in EC cells. This study identified a novel regulatory axis involved in EC from the various aspects of splicing regulation.

In this study, we are going to investigate the effect of nano carbon combined with ex vitro anatomical sorting on the detection rate of lymph nodes (LNs) in gastric cancer (GC) along with the analysis of the correlation between LNs detection rate and patients prognosis. The clinical data of patients undergoing radical gastrectomy in Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University from January 2018 to January 2019 were examined retrospectively. According to whether they adopt nano carbon tracing and specimen sorting method, patients were divided into nano carbon and control groups. The respective rate of detection and correlation of total and positive LNs, respectively, clinical treatment, tumor marker level, and long-term prognosis were matched between these groups. At the same time, the effects of the nano carbon tracer on the detection of total and positive LNs were evaluated. In nano carbon group, more LN specimens could be detected, and the number of positive LNs increased significantly. In addition, in patients with different infiltration stages and LN substations, more LNs could be detected in the nano carbon group for examination, and the detection rate of LNs with diameter less than 5mm was also more. Furthermore, LNs (preferably positive in number) were correlated positively with the attained LNs number. Otherwise, the use of nano carbon suspension could better label LNs in each substation, especially N1 station, and improve micro-LN detection rate. At the same time, the positive metastasis rate in black-stained LNs was higher (31.67 vs. 13.51). In relation to the clinical prognosis, CEAs level, i.e., CA199 and CA125, in the nano carbon group is controlled more effectively. Their condition was not easy to progress and relapse, and their mortality was further reduced. As a result, nano carbon, coupled with ex vitro anatomical sorting, may considerably enhance the detection rate of total and positive LNs, thereby improving the accuracy of clinical staging in GC patients, which has a good influence on their long-term prognosis.

Background: Aberrant fibroblast growth factor 2 (FGF2) expression is a major cause of poor prognosis in pancreatic cancer. MiR-203 is a newly discovered microRNA (miRNA) that can affect the biological behavior of tumors. This study investigated whether miR-203 can regulate FGF2 expression and its role in pancreatic cancer cell proliferation, apoptosis, invasion, and migration. Methods: MiR-203 expression in different cell lines was examined by qRT-PCR, followed by the establishment of knockdown and overexpression cell models. We used the CCK-8 assay to examine cell proliferation and the annexin V-APC/7-AAD double-staining method to detect apoptosis. In addition, we used wound healing and transwell assays to investigate the effects of miR-203 on the migration and invasion of pancreatic cancer cells. The effects of miR-203 knockdown and overexpression on FGF2 mRNA expression were detected by qRT-PCR. We also overexpressed FGF2 and examined the effects of FGF2 overexpression on the proliferation, apoptosis, invasion, and migration of pancreatic cancer cells. The binding of miR-203 to FGF2 was assessed by a luciferase reporter assay. Results: We found that the miR-203 expression level was significantly down-regulated in pancreatic cancer cells compared to normal pancreatic cells. Functionally, the knockdown of miR-203 inhibited cell proliferation and increased apoptosis. Equally important, miR-203 reduced the migration and invasion of pancreatic cancer cells. In addition, we found that miR-203 overexpression inhibited FGF2 expression in pancreatic cancer cells by qRT-PCR. FGF2 overexpression significantly affected the proliferation, invasion, and metastasis of pancreatic cancer cells. Mechanistically, miR-203 base-paired with the FGF2 mRNA, resulting in the knockdown of the FGF2 mRNA and the down-regulation of the FGF2 protein. Conclusions: MiR-203 inhibits FGF2 expression, regulates the proliferation of pancreatic cancer cells, and inhibits the invasion and metastasis of pancreatic cancer cells.