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Zinc finger antisense 1 (ZFAS1), a newly identified long non-coding RNA, is a transcript antisense to the 5' end of the protein-coding gene zinc finger NFX1-type containing 1 which hosts three C/D-box small nucleolar RNAs (SNORDs) within sequential introns: Snord12, Snord12b, and Snord12c. ZFAS1 is dysregulated and acts as either an oncogene or a tumor suppressor in different human malignancies. ZFAS1 has been implicated in many aspects of carcinogenesis, including proliferation, invasion, metastasis, apoptosis, cell cycle, and drug resistance. The mechanisms underlying the effects of ZFAS1 are complex and involve multiple signaling pathways. In this review, the multiple pathological functions of ZFAS1 in diverse malignancies are systematically reviewed to elucidate the molecular basis of its biological roles and to provide new directions for future research.

In a previous study, we showed that transcription factor 21 (TCF21) is methylated and downregulated in human gastric cancer samples and serves as an independent prognostic factor. However, its biological role and potential mechanism in gastric cancer cells remain unexplored. In the current study, we examined TCF21 expression in 6 gastric cancer cell lines. The BGC-823 and SGC-7901 cell lines were selected for small interfering RNA and plasmid transfection, respectively. The results of the Cell Counting Kit-8 assay demonstrated that TCF21 inhibited gastric cancer cell proliferation. Cell cycle analysis suggested that TCF21 inhibited cell cycle progression in gastric cancer cells. The Matrigel invasion assay demonstrated that TCF21 negatively regulated invasion. The cell adhesion assay showed that TCF21 increased cell adhesion. Gastric cancer cells were treated with cisplatin to explore the role of TCF21 in chemoresistance. Cell Counting Kit-8 assay and AnnexinV/propidium iodide analyses showed that TCF21 overexpression sensitized SGC-7901 cells to cisplatin, whereas its depletion reduced sensitivity in BGC-823 cells. JC-1 staining was performed to measure the effect of TCF21 on mitochondrial potential. TCF21 downregulated mitochondrial membrane potential after treatment with cisplatin. Western blot analysis showed that TCF21 overexpression negatively regulated Bcl-xL, phosphorylated extracellular signal regulated kinase, and phosphorylated AKT expression and induced caspase 3 cleavage. LY294002, an AKT inhibitor, blocked the effect of TCF21 on Bcl-xL, caspase 3 and CDDP-induced apoptosis. Nude mice experiments demonstrated that TCF21 inhibited gastric cancer growth in vivo. In conclusion, our results suggest that TCF21 inhibits gastric cancer growth and chemoresistance possibly through the AKT signaling pathway.

The X-inactive-specific transcript (XIST/Xist) is one of the first long non-coding RNAs discovered in mammals and plays an essential role in X chromosome inactivation. XIST is dysregulated and acts as an oncogene or a tumor suppressor in different human malignancies. XIST is implicated in many aspects of carcinogenesis including tumor initiation, invasion, metastasis, apoptosis, cell cycle, stemness, autophagy, and drug resistance. This review focuses on research progress on the roles of XIST in tumor development. The multiple pathological functions of XIST in various cancers are systematically reviewed to elucidate the molecular basis of its biological roles and to provide new directions for future research.

Neurotrophin receptor-interacting melanoma antigen-encoding protein (NRAGE) is a type II melanoma-associated antigen that plays an essential role in various processes, including cell differentiation and apoptosis. NRAGE has been shown to act as a cancer-related protein, with complex and apparently contradictory functions in a variety of cancers. In the current study, we examined the expression of NRAGE protein in 169 gastric cancer samples. NRAGE upregulation was correlated with advanced TNM stage, local invasion, and poor survival. Importantly, NRAGE could serve as an independent prognostic factor in patients with gastric cancer. We also examined the expression of NRAGE protein in GES-1 normal gastric epithelial cells and in six gastric cancer cell lines. Inhibition of NRAGE expression by transfection with small interfering RNA reduced the proliferation and invasion of MGC-803 and HGC-27 cells, as demonstrated by CCK-8 and Matrigel invasion assays. NRAGE depletion also sensitized HGC-27 and MGC-803 cells to cisplatin, as shown by CCK-8 and Annexin V/propidium iodide analyses. Western blot analysis also showed that NRAGE depletion negatively regulated Bcl-2 and p-ERK and upregulated ZO-1 and p27 expression levels. In conclusion, our results suggest that NRAGE acts as a tumor promoter in gastric cancer by facilitating cancer invasion and chemoresistance, possibly through regulation of p-ERK and Bcl-2.