Gastric cancer (GC) is one of the most common cancers in the world. The cathepsin F (CTSF) gene has recently been found to participate in the progression of several types of cancer. However, the clinical characteristics and function of CTSF in GC as well as its molecular mechanisms are not clear. Six GC cell lines and 44 paired adjacent noncancerous and GC tissue samples were used to assess CTSF expression by quantitative polymerase chain reaction (qPCR). We used lentivirus-mediated small hairpin RNA (Lenti-shRNA) against CTSF to knock down the expression of CTSF in GC cells. Western blot and qPCR were used to analyze the mRNA and related protein expression. The biological phenotypes of gastric cells were examined by cell proliferation and apoptosis assays. Microarray-based mRNA expression profile screening was also performed to evaluate the potential molecular pathways in which CTSF may be involved. The CTSF mRNA level was associated with tumor differentiation, depth of tumor invasion, and lymph node metastasis. Downregulation of CTSF expression efficiently inhibited apoptosis and promoted the proliferation of GC cells. Moreover, a total of 1,117 upregulated mRNAs and 1,143 downregulated mRNAs were identified as differentially expressed genes (DEGs). Further analysis identified the involvement of these mRNAs in cancer-related pathways and various other biological processes. Nine DEGs in cancer-related pathways and three downstream genes in the apoptosis pathway were validated by Western blot, which was mainly in agreement with the microarray data. To our knowledge, this is the first report investigating the effect of CTSF on the growth and apoptosis in GC cells and its clinical significance. The CTSF gene may function as a tumor suppressor in GC and may be a potential therapeutic target in the treatment of GC.
Purpose
Dysregulation of miR‐148a‐3p in gastric cancer was reported. However, the diagnostic potential and biological function of miR‐148a‐3p in gastric cancer progression is not fully studied.
Methods
Bioinformatics analysis and RT‐qPCR assay were performed to analyze the expression of miR‐148a‐3p in gastric cancer tissues and plasma of gastric cancer patients. Receiver operating characteristic curve analysis was performed to analyze the diagnostic value of miR‐148a‐3p. In vitro proliferation, apoptosis, migration, invasion, sphere formation assay and Western blotting assay were performed to evaluate the biological function of miR‐148a‐3p in gastric cancer progression.
Results
miR‐148a‐3p was significantly down‐regulated in both gastric cancer patients' tissue and plasma samples. Plasma miR‐148a‐3p showed promising efficacy for gastric cancer diagnosis. Overexpression of miR‐148a‐3p could inhibit the proliferative phenotype, metastatic phenotype, and cancer stem‐like properties of gastric cancer cells.
Conclusions
miR‐148a‐3p inhibits cancer progression and is a novel diagnostic biomarker for gastric cancer.
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