Abstract

Long non-coding RNAs contribute to the development of human cancers. We compared the long non-coding RNA levels in gastric cancer (GC) and para-cancerous tissues in the Gene Expression Omnibus, and found that small nucleolar RNA host gene 12 (SNHG12) was upregulated in GC tissues. Fluorescence in situ hybridization confirmed that SNHG12 is overexpressed in GC tissues. We then used data from The Cancer Genome Atlas to assess the association of SNHG12 expression with the clinicopathological characteristics and prognosis of GC patients and found that higher SNHG12 expression was associated with a greater tumor invasion depth and poorer survival. In vitro, silencing SNHG12 suppressed GC cell proliferation, migration and invasion, but induced apoptosis and cell cycle arrest. Overexpressing SNHG12 had the opposite effects. In xenografted mice, knocking down SNHG12 reduced GC tumor growth. Taken together, cancer pathway microarray and bioinformatics analyses, RNA pulldown assays, Western blotting and immunohistochemistry revealed that SNHG12 induces GC tumorigenesis by activating the phosphatidylinositol 3-kinase/AKT pathway. SNHG12 may thus be a useful marker for predicting poor survival in GC patients.

Highlights

  • According to the global cancer statistics released in 2018, gastric cancer (GC) is the fifth most commonly diagnosed cancer type and the third leading cause of cancer-related mortality worldwide [1]

  • We focused our attention on upregulated long non-coding RNAs (lncRNAs), as they may be more suitable than downregulated lncRNAs for use as early diagnostic markers in cancer patients [2]

  • SNHG5 is a tumor suppressor in GC [26, 27], SNHG8 predicts a poor prognosis in GC patients [28] and SNHG17 induces the development of GC [29]

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Summary

Introduction

According to the global cancer statistics released in 2018, gastric cancer (GC) is the fifth most commonly diagnosed cancer type and the third leading cause of cancer-related mortality worldwide [1]. Whole-genome sequencing has revealed that over 90% of the genome is actively transcribed, but 98% of the transcripts have no potential to encode proteins [3]. Among these non-coding transcripts, long non-coding RNAs (lncRNAs), which include at least 200 nucleotides, have attracted more and more attention [4]. The dysregulation of lncRNAs is involved in a range of diseases, including cancers [6,7,8]. LncRNAs have been reported to promote the growth, metastasis and drug resistance of cancer cells [9,10,11]

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