<p>The lncRNA ZEB2-AS1 is upregulated in gastric cancer and affects cell proliferation and invasion via miR-143-5p/HIF-1&alpha; axis</p>

Abstract

BackgroundGrowing evidence has implicated the important role of the long non-coding RNAs (lncRNAs) in gastric cancer progression. In this study, we examined the expression of lncRNA zinc finger E-box-binding homeobox 2 antisense RNA 1 (ZEB2-AS1) in gastric cancer tissues and elucidated the molecular mechanisms underlying ZEB2-AS1-mediated gastric cancer progression.MethodsQuantitative real-time PCR measured the gene expression level; CCK-8, colony formation and cell invasion assays determined gastric cancer cell proliferation, growth and invasion, respectively; the xenograft nude mice model was used to determine in vivo tumor growth; Bioinformatics analysis and luciferase reporter assay determined the downstream targets of ZEB2-AS1 and miR-143-5p. The expression of ZEB2-AS1 was upregulated in gastric cancer cell lines.ResultsKnockdown of ZEB2-AS1 suppressed gastric cancer cell proliferation, growth and invasion, and also suppressed in vivo tumor growth in the nude mice. Overexpression of ZEB2-AS1 potentiated gastric cancer cell proliferation, growth and invasion. Bioinformatics analysis and luciferase reporter assay showed that miR-143-5p was a direct target of ZEB2-AS1 and was negatively regulated by ZEB2-AS1. Furthermore, hypoxia-inducible factor-1α (HIF-1α) was found to be a target of miR-143-5p and was negatively regulated by miR-143-5p. The rescue in vitro assays showed that the effects of ZEB2-AS1 overexpression on gastric cancer cell proliferation, growth and invasion was mediated via miR-143-5p/HIF-1α. ZEB2-AS1 and HIF-1α was upregulated in gastric cancer tissues, while miR-143-5p was down-regulated; and ZEB2-AS1 expression level was inversely correlated with miR-143-5p expression level, and positively correlated with HIF-1α mRNA expression level; while miR-143-5p expression level was inversely correlated with HIF-1α expression level. High ZEB2-AS1 expression level was correlated with poor differentiation, lymph node metastasis and distant metastasis.ConclusionCollectively, our results indicated that ZEB2-AS1 was up-regulated in gastric cancer tissues and cells and promoted cell proliferation and metastasis through miR-143-5p/HIF-1α pathway, which may provide a promising target for treatment of gastric cancer.

Over-expression of long non-coding RNA ZEB2-AS1 may predict poor prognosis and promote the migration, invasion, and epithelial-mesenchymal transition of tumor cells in non-small cell lung cancer

“…Uncontrolled growth and increased migration and invasion ability are the most important features of the tumor cells. 14,22 ZEB2-AS1 was reported to promote the proliferation and migration of different type of cancer cells 14,23,24, and in the present study, we found that the knockdown of ZEB2-AS1 inhibits the viability of A549 cells, which is consistent with Guo et al’s observation. 12 In contrast, ZEB1-AS1 has been found to induce N-cadherin and inhibit E-cadherin transcription.…”

“…ZEB2-AS1 is a recently identified lncRNA, and the roles of ZEB2-AS1 in different types of cancers have been discussed in several previous studies. For example, Diao et al 13 suggested that increased expression of ZEB2-AS1 may promote EMT and metastasis of neck squamous cell carcinoma cells; Wu et al 14 found that ZEB2-AS1 is over-expressed in gastric cancer, and that it may affect the proliferation and invasion of gastric cancer cells via targeting miR-143-5p/HIF-1α axis; Gao et al 15 reported that ZEB2-AS1 can promote the growth and invasion of pancreatic cancer cells via targeting the miR-204/HMGB1 axis; and Lan et al 16 suggested that ZEB2-AS1 can regulate the proliferation and metastasis of hepatocellular carcinoma cells. In NSCLC, Guo et al 12 reported that ZEB2-AS1 was up-regulated in NSCLC and may promote proliferation, and inhibit the apoptosis, of NSCLC cells in vitro.…”

Long-Noncoding RNA (lncRNA) in the Regulation of Hypoxia-Inducible Factor (HIF) in Cancer

“…Apart from PVT1 [42,43], various other lncRNAs exert their regulatory function on HIF-1α by acting as ceRNAs [72][73][74][75][76][77][78][79][80][81][82][83][84][85][86][87][88][89][90]. See Table 2 for an overview of ceRNAs and their associated pathways in HIF regulation.…”

The Roles of Hypoxia-Inducible Factors and Non-Coding RNAs in Gastrointestinal Cancer

“…Therefore, miR-186 functions as a tumor suppressor in GC. HIF-1α expression is also negatively regulated by miR-143-5p, but is positively correlated with the expression of the lncRNA ZEB2-AS1 in GC [25]. Bioinformatic analysis has revealed that ZEB2-AS1 can be regulated by miR-143-5p; therefore, ZEB2-AS1-mediated GC progression may involve the miR-143-5p/HIF-1α axis.…”

“…Promotes apoptosis and reduces cell invasion by regulating HIF-1α HIF-1α [23] miR-186 Directly regulates HIF-1α and inhibits cell proliferation HIF-1α [24] miR-143 Directly regulates HIF-1α HIF-1α, ZEB2-AS1 [25] PVT1 Enhances multidrug resistance and is associated with lymph node metastasis HIF-1α, MDR1, MRP, mTOR [26,27] miR-320 Upregulated by crocin and regulates HIF-1α by inhibiting KLF5 KLF5 [28] miR-210…”