Objective: Colon cancer (CC) is a prevalent malignancy with unfavorable prognosis, highly latent in the early phase. Its prevention and treatment primarily lies in accessible effective blood markers. This study was for analyzing the clinical value of SOX2OT in CC to offer dependable reference and guidance for future clinical practice. Methods: Totally 74 patients with CC in our hospital between May 2014 and June 2015 were enrolled, and 68 healthy individuals were also enrolled meantime. SOX2OT in their serum and tissues was quantified, and its association with the development/progression/metastasis of CC was studied. All patients were followed up for 5 years for analyzing the value of SOX2OT for cases with CC. Results: With a high concentration in the serum and cancer tissues of patients with CC, SOX2OT possessed a high value in forecasting the development/progression/metastasis of CC. Additionally, with a decrease after treatment, it performed remarkably in forecasting the death of patients, and its increase foretold an increased risk of death. Conclusion: SOX2OT possesses a high value in forecasting the development/progression/metastasis of CC, and its high level foretells a raised risk of unfavorable prognosis.

Intrahepatic cholangiocarcinoma is a malignant tumor originating from intrahepatic bile ducts. Surgical therapy, radiotherapy, and chemotherapy are taken to treat this disease, but it is prone to recurrence and metastasis, with poor prognosis. Therefore, it is of great significance to explore new targets and molecular mechanisms for the development of cholangiocarcinoma cells. Clinical cholangiocarcinoma tissues from patients and four human cholangiocarcinoma cell lines were analyzed for microRNA-373 (miR-373) expression. For investigating whether miR-373 directly modulated unc-51 like autophagy activating kinase 1 (ULK1), dual-luciferase reporter assay was performed. In addition, CCK-8 assay, flow cytometry, western blot, and immunofluorescence were applied to evaluate the proliferation, apoptosis, and autophagy of cholangiocytic hepatocellular carcinoma cells. miR-373 downregulation was observed in clinical tissues and cell lines of cholangiocarcinoma. Overexpression of miR-373 reduced proliferation, enhanced apoptosis, and raised expression levels of pro-apoptosis proteins including BCL2 associated X (Bax), Caspase-3, and Caspase-9. Moreover, overexpression of miR-373 downregulated expression levels of microtubule-associated protein 1A/1B-light chain 3 (LC3)-II, Beclin-1, and promoted P62 expression on mRNA and protein levels. After miR-373 knockdown, all indexes of apoptosis and autophagy mentioned above were reversed. Luciferase activity was decreased after cotransfection of miR-373 mimic and wild-type ULK1 vector. Also, miR-373 overexpression inhibited ULK1 expression. Importantly, overexpression of miR-373 weakened expressions of ULK1, LC3, Beclin-1, and Bcl-2, and enhanced expressions of P62, Bax, Caspase-3, and Caspase-9. miR-373 mimic treatment and subsequent ULK1 overexpression, induced reverse regulation in expressions of these proteins, compared with overexpression of miR-373 only. miR-373 targeted ULK1 to initiate inhibition of autophagy and subsequent promotion of apoptosis in cholangiocarcinoma cells.

Long non-coding RNAs (lncRNAs) can act as carcinogenic or cancer suppressive factors during the pathogenesis, invasion and metastasis of non-small cell lung cancer (NSCLC). The current study explored the role of long intergenic non-protein coding RNA 00887 (LINC00887) and competing endogenous RNAs (ceRNAs). It was revealed that LINC00887 interacts with several microRNAs (miRs), which regulates downstream genes such as fibronectin 1, MET proto-oncogene, receptor tyrosine kinase and mothers against decapentaplegic homolog 4, which are associated with the spread of lung cancer. The experimental results also suggested that LINC00887 can stimulate miR-613, miR-206 and miR-1-2 to become competing endogenous RNAs, which may regulate the epithelial-mesenchymal transition of NSCLC cells through the transforming growth factor-a signal transduction pathway, and therefore promote the migration of cells and the acquisition of stem cell characteristics. Therefore, it can be concluded that high levels of LINC00887 can accelerate the malignant transformation ability of NSCLC cells.

This study aimed to assess mRNA and lncRNA expression differences between lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD). Cancer tissues were obtained from three LUSC and three LUAD patients, followed by RNA-seq. Differentially expressed mRNAs (DE-mRNAs) and lncRNAs (DE-lncRNAs) were identified between LUSC and LUAD, after which functional enrichment analysis and protein-protein interaction (PPI) network construction was performed on DEGs. Coexpression analysis of lncRNA-gene and prediction of DEG-related miRNAs as well as function enrichment analysis, and construction of competing endogenous RNAs (ceRNA) regulatory network were then conducted. Moreover, survival analysis on differentially expressed RNAs was performed based on data downloaded from The Cancer Genome Atlas (TCGA) database. In this study, 518 DEGs and 117 DE-lncRNAs were identified between LUSC and LUAD. The DEGs were mainly associated with cell adhesion, PI3K-Akt signaling pathway, and focal adhesion. PPI network analysis indicated several genes with highest connectivity, such as CCND1. DE-lncRNAs that coexpressed with DEGs were also associated with tight junction and DE-lncRNAs that had more corepressed relationships with DEGs included GSEC, NKX2-1-AS1, LINC01415, and LINC00839. Moreover, the genes and lncRNAs with higher connectivity in the ceRNA network included NEAT1, SLC5A3, LINC00839, ETV1, CMTM4, and SNX30. Several genes were significantly related to the survival of patients with LUSC and LUAD, including ETV1, RTKN2, SNX30, PAK2, and CCND1. Genes and lncRNAs associated with cell junction have specific patterns in two major histological subtypes of NSCLC. GSEC, NKX2-1-AS1, NEAT1, CCND1, and ETV1 may be potential novel biomarkers for personalized treatment strategies of NSCLC.

Long non-coding RNAs (lncRNAs) can act as carcinogenic or cancer suppressive factors during the pathogenesis, invasion and metastasis of non-small cell lung cancer (NSCLC). The current study explored the role of long intergenic non-protein coding RNA 00887 (LINC00887) and competing endogenous RNAs (ceRNAs). It was revealed that LINC00887 interacts with several microRNAs (miRs), which regulates downstream genes such as fibronectin 1, MET proto‐oncogene, receptor tyrosine kinase and mothers against decapentaplegic homolog 4, which are associated with the spread of lung cancer. The experimental results also suggested that LINC00887 can stimulate miR-613, miR‐206 and miR‐1‐2 to become competing endogenous RNAs, which may regulate the epithelial-mesenchymal transition of NSCLC cells through the transforming growth factor-â signal transduction pathway, and therefore promote the migration of cells and the acquisition of stem cell characteristics. Therefore, it can be concluded that high levels of LINC00887 can accelerate the malignant transformation ability of NSCLC cells.

Aberrant microRNA (miRNA or miR) expression has been reported to contribute to the pathogenesis of hepatocellular carcinoma (HCC). However, the involvement of specific miRNAs in HCC remains to be elucidated. The present study aimed to investigate the potential role of miR-200b and the mechanism underlying its function in hepatocarcinogenesis. The results of the present study demonstrated that the expression levels of miR‑200b were significantly reduced in HCC tissue samples, as compared with normal liver (NL) and para‑tumorous (PT) tissue samples. The results also revealed that miR‑200b expression levels in HepG2 cells were significantly decreased compared with those in L02 cells. In addition, western blotting and reverse transcription‑quantitative polymerase chain reaction demonstrated that the expression levels of DNA methyltransferase 3a (DNMT3a), a possible target gene for miR‑200b, were significantly higher in HCC tissue samples, as compared with those in NL and PT tissue samples. Furthermore, the data suggested that DNMT3a was a direct target gene of miR‑200b. Upregulated miR‑200b expression in HepG2 cells led to a decrease in DNMT3a expression levels, and an inhibition of cell proliferation. These results suggested that miR‑200b has an important role in hepatocarcinogenesis and acts by downregulating DNMT3a expression. Thus, miR-200b may be a promising target for HCC treatment.

A class of adhesion protein that occurs in the membrane with both extracellular and intracellular domain and play vital role in maintaining multicellularity is TRASK, also called CUB-domain containing protein1, CD318 (CDCP1). Specifically, in the current study, documented aggressive grades of lung cancers and distant metastatic tissues were examined for protein interactions of Trask and compared with lung cancer variants in situ. The intracellular domain of Trask has the ability to undergo tyrosine phosphorylation and thereafter undergo increased genomic expression, as well as interact with cytoskeletal proteins in the cell periphery and other local signal transduction machinery to induce invadopodia formation and distant metastasis. We incorporated proximity ligation assay to examine protein interactions of Trask in metastatic lung cancer tissues and compare with advanced and low-grade lung cancers restricted to the primary site of origins. Here, we provide direct evidence that activated Trask, which is a phosphorylated form, binds with cytoskeletal proteins actin and spectrin. These interactions were not seen in locally growing lung cancer and cancer in situ. These interactions may be responsible for invadopodia formation and breaking free from a multicellular environment. Functional studies demonstrated interaction between Trask and the STOCs Orai1 and Stim1. Calcium release from internal stores was highest in metastatic lung cancers, suggesting this mechanism as an initial stimulus for the cells to respond chaotically to external growth factor stimulation, especially in aggressive metastatic variants of lung cancers. Recently, inhibitors of STOCs have been identified, and preclinical evidence may be obtained whether these drugs may be of benefit in preventing the deadly consequences of lung cancer.