Abstract
Cisplatin (DDP) resistance is a huge obstacle to gastric cancer (GC) treatment. Long non-coding RNAs (lncRNAs) have been manifested to exert pivotal functions in GC development. Herein, we aimed to explore the functional impact of lncRNA small nucleolar RNA host gene 6 (SNHG6) on DDP resistance and progression of GC. Quantitative real-time PCR (qRT-PCR) assay or Western blotting was performed to detect the expression of SNHG6, microRNA(miR)-1297, and epithelial–mesenchymal transition (EMT)-related factors and B-Cell Lymphoma 2 (Bcl-2) in DDP-resistant GC cells. Half inhibition concentration (IC50) to DDP, clonogenicity, apoptosis and invasion were examined via CCK-8 assay, colony formation assay, flow cytometry and Transwell assay, respectively. Target association between miR-1297 and SNHG6 or BCL-2 was demonstrated via dual-luciferase reporter assay or RIP assay. Xenograft models in nude mice were formed to investigate role of SNHG6 in vivo. We found that SNHG6 and BCL-2 were up-regulated, while miR-1297 expression was declined in GC tissues and DDP-resistant cells. Moreover, depletion of SNHG6 or gain of miR-1297 could repress DDP resistance, proliferation and metastasis of DDP-resistant cells, which was weakened by miR-1297 inhibition or BCL-2 overexpression. Besides, SNHG6 positively regulated BCL-2 expression by sponging miR-1297. Furthermore, SNHG6 knockdown repressed GC tumor growth in vivo. In a word, lncRNA SNHG6 knockdown had inhibitory effects on DDP resistance and progression of GC by sponging miR-1297, highlighting its potential in GC treatment.
Highlights
Gastric cancer (GC) is a most common tumor around the world, serving as third contributor of malignancy-associated deaths [1]
Determination of long non-coding RNA (lncRNA) Small nucleolar RNA host gene 6 (SNHG6) expression in GC tissues and cells Quantitative real-time PCR (qRT-PCR) assay presented that SNHG6 expression was apparently elevated in GC tissues in reference to normal tissues (Figure 1A)
The obvious upregulation of SNHG6 was discovered in GC cells in comparison with GES-1 cells, especially in DDP-resistant cells (AGS/DDP and MKN-45/DDP) compared with their parental DDP-sensitive cells (Figure 1C)
Summary
Gastric cancer (GC) is a most common tumor around the world, serving as third contributor of malignancy-associated deaths [1]. Many novel approaches have applied to GC treatment [2], the 5-year survival remains very poor due to lack of biomarker and cell resistance to chemotherapy agents, such as cisplatin (DDP) [3,4]. Deeper exploration on the mechanistic pathway of GC tumorigenesis and DDP resistance is greatly significant. Long non-coding RNAs (lncRNAs) are a category of non-protein-coding RNAs with lengths exceeding 200 nucleotides (nts) and act as important regulators in cancer development owing to their specific roles in tumorigenesis and metastasis by mediating gene transcription and post-transcriptional modification. Small nucleolar RNA host gene 6 (SNHG6) is deemed as a promising prognostic biomarker of many human cancers and has close association with several clinicopathological characteristics [10]. SNHG6, an oncogene in GC, is demonstrated to be a potent prognostic
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