Abstract

Patients with advanced gastric cancer (GC) have a poor prognosis with a median overall survival of 10–12 months. Long non-coding RNA nicotinamide nucleotide transhydrogenase-antisense RNA1 (NNT-AS1) and sex-determining region Y-related high mobility group box 4 (SOX4) have been reported to be associated with the progression of various types of cancer; however, the regulatory mechanism between NNT-AS1 and SOX4 in GC is not completely understood. Reverse transcription-quantitative PCR was used to detect the expression levels of NNT-AS1, microRNA (miR)-142-5p and SOX4. Western blotting was performed to assess the protein expression levels of SOX4, β-catenin, c-Myc, Bcl-2 and E-cadherin. The proliferation, apoptosis, migration and invasion of GC cells were determined using MTT, flow cytometry and Transwell assays. The relationship between miR-142-5p and NNT-AS1 or SOX4 was investigated using a dual-luciferase reporter assay. NNT-AS1 and SOX4 were upregulated, whereas miR-142-5p was downregulated in GC tissues and cells compared with normal tissues and cells. Both NNT-AS1 and SOX4 knockdown inhibited GC cell proliferation, migration and invasion, and enhanced GC cell apoptosis. Moreover, the results indicated that NNT-AS1 modulated SOX4 expression by sponging miR-142-5p. In addition, SOX4 overexpression reversed NNT-AS1 knockdown-mediated effects on GC cell proliferation, apoptosis, migration and invasion. NNT-AS1 knockdown blocked the Wnt/β-catenin signaling pathway via the miR-142-5p/SOX4 axis. Collectively, the present study indicated that NNT-AS1 knockdown decreased GC cell proliferation, migration and invasion, and induced GC cell apoptosis by regulating the miR-142-5p/SOX4/Wnt/β-catenin signaling pathway axis.

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