In this study, we found that H19 expression was significantly increased in HP-infected GC tissues and cells. Furthermore, we demonstrated that HP induced GC cell migration, invasion and inflammatory response. Moreover, our results identified for the first time that H19 promoted proliferation, migration and invasion of HP-induced GC cells via activating the NF-κB signaling pathway. These results increase our understanding on the role of the H19 in GC with HP infection. HP is considered to be a major risk factor of GC. Our data revealed that HP infection promoted GC cell viability, migration and invasion, and up-regulated pro-inflammatory cytokines including TNF-α, IL-1β, IL-6 and IL-8. These results are in agreement with other studies [
21,
22]. These cytokines are considered important mediators of gastric pathophysiology and may play critical roles in the development of gastric inflammation and GC. It has been reported that activation of NF-κB and up-regulation of IL-8 in GC cells were suggested as the critical mechanisms responsible for HP-induced chronic inflammation and gastric carcinogenesis [
23]. HP may activate NF-κB signaling through classical or alternative pathways, depending on the cell type. Activation of NF-κB by HP in gastric epithelial cells was mainly through the classical pathway, which is dependent on CagA (cytotoxin-associated gene A) and its pathogenicity island [
8]. Nowadays, numerous lncRNAs have been reported to play important roles in carcinogenesis at both transcriptional and post-transcriptional levels, but their specific mechanisms of action still remain elusive [
24,
25]. H19 has been identified as one of the lncRNAs involved in tumorigenesis, however, its role in tumor proliferation has been controversial for a long time. A previous study implied that H19 may function as a tumor suppressor [
26]. However, other studies provided conflicting evidence as to whether H19 can promote GC and thyroid cancer [
27]. In our study, H19 was expressed at higher levels in HP-infected GC tissues than in adjacent tissues, and promoted the proliferation, migration, and invasion of GC cells, which is consistent with other recent studies [
28,
29]. We further demonstrated that H19 promoted the proliferation, migration and invasion of HP-infected GC cells via activating the NF-κB signaling pathway. Studies have shown that NF-κB inhibitors including BAY11–7082 and PDTC indeed directly affected GC cell growth [
30‐
32]. However, in this study, we found that the reversal effect of NF-κB inhibitors on H19-mediated GC growth was dependent on HP infection. Our previous study showed that H19/miR-675 axis promotes GC via Fas-associated death domain protein (FADD)/caspase-8/caspase-3 signaling pathway [
19]. FADD/caspase-8/caspase-3 signaling pathway was an important pathway regulating cell apoptosis whereas the NF-κB is an important mediator regulating inflammation [
33]. Evidence has indicated that FADD, caspase-8-related protein (Casper), and pro-caspase-8 are parts of the tumor necrosis factor receptor type 1 (TNF-R1) -induced NFκB activation pathways, whereas activated caspase-8 can negatively regulate TNF-R1-induced NF-κB activation [
34]. Further investigation was required to explore the relationship between NF-κB and FADD/caspase-8/caspase-3 signaling in the context of GC.