Ion channels are involved in regulating cell proliferation and apoptosis (programed cell death). Since increased cellular proliferation and inhibition of apoptosis are characteristic features of tumorigenesis, targeting ion channels is a promising strategy for treating cancer. CLC-3 is a member of the voltage-gated chloride channel superfamily and is expressed in many cancer cells. In the plasma membrane, CLC-3 functions as a chloride channel and is associated with cell proliferation and apoptosis. CLC-3 is also located in intracellular compartments, contributing to their acidity, which increases sequestration of drugs and leads to chemotherapy drug resistance. In this review, we summarize the recent findings concerning the involvement of CLC-3 in cancer and explore its potential in cancer therapy.

To explore the role of long-chain non-coding RNA (lncRNA) taurine up-regulated gene 1 (TUG1) in the development of colorectal cancer (CRC) via the miR-138-5p/zinc finger E-box-binding homeobox 2 (ZEB2) axis. Eighty-four CRC tissue specimens and 84 corresponding paracancerous tissue specimens were sampled from 84 patients with CRC admitted to the First Hospital of Jilin University from January 2018 to September 2019. The TUG1 expression in the specimens was determined, and its value in diagnosis and prognosis of CRC was analyzed. Additionally, constructed stable and transient overexpresison vectors and inhibition vectors were transfected into CRC cells. The MTT, transwell, and flow cytometry were adopted for analysis on the proliferation, invasion, and apoptosis of transfected cells, respectively, and a dual luciferase reporter (DLR) assay was carried out for correlation determination between TUG1 and miR-138-5p and between miR-138-5p and ZEB2. TUG1 was up-regulated in CRC, and serum TUG1 could be adopted as a diagnostic marker of CRC, with area-under-the-curve (AUC) larger than 0.8. In addition, siRNA-TUG1, shRNA-TUG1, miR-138-5p-mimics, and miR-138-5p-inhibitor were transfected into cells, and it turned out that overexpressing miR-138-5p and inhibiting ZEB2 exerted the same effects. The DLR assay revealed that TUG1 was able to targetedly regulate miR-138-5p, and miR-138-5p could targetedly regulate ZEB2, and in vitro experiments revealed that TUG1 could affect the epithelial-to-mesenchymal transition (EMT) of CRC via the miR-138-5p/ZEB2 axis. TUG1 could promote the development of CRC via the miR-138-5p/ZEB2 axis.

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Background: Most recently, long non-coding RNAs (lncRNAs) emerge as crucial modulators in many biological processes, such as embryonic development, cell growth, and tumorigenesis. However, the correlations between lncRNAs and colorectal cancer (CRC) cell proliferation, metastasis, and gemcitabine resistance are not well understood. Results: The expression of AGAP2-AS1 was overexpressed in CRC tissues and negatively correlated with the survival of patients with CRC. AGAP2-AS1 promoted CRC cell proliferation and inhibited apoptosis. Moreover, AGAP2-AS1 enhanced the chemoresistance of CRC cells to gemcitabine. In addition, AGAP2-AS1 enhanced the migration and invasion of CRC cells. Mechanistic studies showed that AGAP2-AS1 regulated fibroblast growth factor receptor 1 (FGFR1) expression by sponging miR-497 in CRC progression. Conclusion: We identified an oncogenic role of AGAP2-AS1 in the development and progression of CRC. Methods: qRT-PCR was used to measure the expression of AGAP2 Antisense RNA 1 (AGAP2-AS1) in 116 cases of CRC and adjacent normal tissues. Luciferase reporter assays was used to detect the interaction between AGAP2-AS1 and miR-497. The xenograft tumor experiment was used to study the in vivo function of AGAP2-AS1.

Colorectal cancer is one of the most common malignant tumors with a high rate of distant metastasis, postoperative recurrence and mortality. ATPase family AAA domain-containing protein 2 (ATAD2), a member of ATPase family, is highly expressed in various cancers, including colorectal cancer. However, whether ATAD2 plays a role in the migration and invasion of colorectal cancer cells remains unknown. In this study, we established ATAD2 knockdown in colorectal cancer cell lines by RNA interference and found that silencing of ATAD2 inhibited the migration and invasion ability of Caco-2 and SW-480 cells. Moreover, ATAD2 silencing suppressed epithelial-mesenchymal transition (EMT), and reduced the expression and enzymatic activity of matrix metalloproteinases (MMPs) in Caco-2 and SW-480 cells. In summary, our results suggest that silencing of ATAD2 inhibits migration and invasion of colorectal cancer cells by suppressing EMT and decreasing the activity of MMPs. Hence, ATAD2 could be considered as a novel molecular marker of metastatic colorectal cancer, and it may provide new insights for clinical diagnosis and treatment of colorectal cancer.

To investigate the role of microRNA-497-5p (miR-497-5p) in the tumorigenesis of colorectal cancer (CRC), the present study applied qRT-PCR to detect the expression level of miR-497-5p in both clinical samples and CRC cell lines. Furthermore, to specifically evaluate the carcinogenic role of miR-497-5p in CRC, the expression of miR-497-5p was monitored by transfecting with the mimics or inhibitors of miR-497-5p. Transwell assay as well as CCK-8 assay were used to determine the functions of miR-497-5p on cell invasion, migration and proliferation, respectively. miR-497-5p expression was remarkably down-regulated in clinical samples with cancer development as well as in CRC cell lines. Additionally, low miR-497-5p expression was remarkably correlated with higher TNM stage and lymph node metastasis of CRC patients. Up-regulation of miR-497-5p significantly inhibited proliferation, migration, and invasion of LOVO CRC cell line. Conversely, antagonizing miR-497-5p significantly promoted cell proliferation, migration and invasion. Mechanistic analysis revealed that miR-497-5p directly bound to its downstream target, protein tyrosine phosphatase non-receptor type 3 (PTPN3), whose aberrant expression partially reversed inhibition of cell proliferation and migration. Taken together, the present study elucidated the inhibitory role of miR-497-5p in CRC via targeting PTPN3, which potentiated miR-497-5p as a potential therapeutic target for combating CRC.

Abstract. Glioblastoma multiforme (GBM) is the most malignant type of human glioma, and has a poor prognosis. Screening differentially expressed genes (DEGs) in brain tumor samples and normal brain samples is of importance for identifying GBM and to design specific-targeting drugs. The transcriptional profile of GSE30563, containing three genechips of brain tumor samples and three genechips of normal brain samples, was downloaded from Gene Expression Omnibus to identify the DEGs. The differences in the expression of the DEGs in the two different samples were compared through hierarchical biclustering. The co-expression coefficient of the DEGs was calculated using the information from COXPRESdb, the network of the DEGs was constructed and functional enrichment and pathway analysis were performed. Finally, the transcription factors of important DEGs were predicted. A total of 1,006 DEGs, including 368 upregulated and 638 downregulated DEGs, were identified. A close correlation was demonstrated between six important genes, associated with immune response, HLA-DQB1, HLA-DRB1, HLA-DPA1, HLA-B, HLA-DMA and HLA-DRA, and the immune response. Allograft rejection was selected as the most significant pathway. A total of 17 transcription factors, including nuclear factor (NF)-κB and NF-κB1, and their binding sites containing these six DEGs, were also identified. The DEGs, including major histocompatibility complex (MHC) class II, DQβ1, MHC class II, DRβ1, MHC class IB, MHC class II, DMα, MHC class II, DPα1, MHC class II, DRα, may provide novel targets for the diagnosis and treatment of GBM. The transcription factors of these six genes and their binding sites may also provide evidence and direction for identifying target-specific drugs.

This study aims to explore the expression and degree of methylation of lncRNA MEG3 in gastric cancer tissues and to analyze its effect on the migration and proliferation of gastric cancer patients and the mechanism by which this occurs. The targeting relationship between MEG3, miR-181a-5p and ATP4B was detected through molecular biology experiments. Wound healing, transwell, colony formation and flow cytometry assays were used to analyze the effects of lncRNA MEG3 and methylation on tumor cell migration, invasion, proliferation and apoptosis. In addition, a tumor xenotransplantation model was established to study the influence of MEG3 on tumor growth in vivo. Bioinformatics analysis showed that lncRNA MEG3 and ATP4B were downregulated in gastric cancer tissues compared with normal tissues. Bioinformatics predicted that ATP4B might be regulated by targeting miR-181a-5p. The overexpression of MEG3 and the application of 5-Aza treatment inhibited the migration, invasion and proliferation of MGC-803 cells and promoted apoptosis. In gastric cancer tissues, MEG3 is hypermethylated to decrease expression. Once the expression of MEG3 is restored or methylation is inhibited, tumor growth can be inhibited both in vivo and in vitro. This finding could be utilized as a clinical reference for gastric cancer treatment in the future.