Upregulation of H19 promotes invasion and induces epithelial-to-mesenchymal transition in esophageal cancer

Abstract

Abstract. Long non-coding RNAs (lncRNAs) have previously been reported to be involved in cancer invasion, proliferation and apoptosis. However, the association between the lncRNA, H19, and esophageal cancer (EC) has remained elusive. In the present study, reverse transcription quantitative-polymerase chain reaction revealed that the expression of H19 was significantly increased and associated with tumor depth and metastasis in 133 EC samples. Furthermore, MTT and Transwell assays revealed that overexpression of H19 in vitro promoted the proliferation and invasion of EC cell lines, whereas knockdown of H19 inhibited the proliferation and invasion of EC cell lines. In addition, it was identified that an upregulation of H19 induced epithelial-to-mesenchymal transition, while the opposite effect was observed following the downregulation of H19. In conclusion, H19 has a significant role in the development of EC and may serve as a potential prognostic marker and therapeutic target for EC. IntroductionEsophageal carcinoma (EC) is the eighth most aggressive and malignant type of cancer, with a high incidence that varies according to geographic location and ethnicity (1). Despite progress in the development of diagnostic and therapeutic options, the survival rates for EC patients remain poor. Therefore, the identification of novel genes involved in the tumorigenesis and development of EC is urgently required.Long non-coding RNAs (lncRNAs) are a class of RNAs that have been reported to be involved in the regulation, invasion, proliferation and apoptosis of multiple tumors (2,3). The association between H19 expression and the progression of various types of cancer has been demonstrated in previous studies. One study found that the overexpression of lncRNA H19 enhanced the carcinogenesis and metastasis of gastric cancer (4). MALAT-1, an abundant lncRNA present in many human cell types, has been suggested to regulate the alternative splicing of a subset of pre-messenger (m)RNAs by modulating serine/arginine splicing factor activity. This factor in turn regulates tissue or cell-type-specific alternative splicing in a phosphorylation-dependent manner (5). However, the role of H19 in EC is yet to be elucidated.The epithelial-to-mesenchymal transition (EMT) has an important role in the invasion of various types of cancer by transforming adherent and polarized epithelial cells into invasive and motile mesenchymal cells (6,7). A number of transcription factors involved in EMTs, including Twist and Snail, increase the expression level of mesenchymal markers, including fibronectin, collagen and Vimentin, and decrease the expression of epithelial markers, including E-cadherin. The breakdown of tight junctions results in the loss of epithelial markers and the acquisition of mesenchymal markers (8-10).In the present study, the expression levels of H19 in EC were investigated, in order to elucidate the role of H19 in EC. Materials and methods Clinical

Integrated analysis of long non-coding RNA competing interactions reveals the potential role in progression of human gastric cancer

“…The ceRNA network we built reveals an unknown ceRNA regulatory network in GC. Recent study also identified that lncRNA interactions with miRNA and mRNA might act as potential diagnosis and prognosis biomarkers in cancer, such as H19, PVT1, HOTAIR, UCA1 and TINCR (7,(48)(49)(50)(51). In our ceRNA network, we also found these key lncRNAs.…”

mRNA and methylation profiling of radioresistant esophageal cancer cells: the involvement of Sall2 in acquired aggressive phenotypes

“…Notably, multiple CpG sites of noncoding RNA H19 (lncRNA-H19) were demethylated in radiation-resistant cells, indicating activation of its expression. Upregulation of H19 promotes invasion, induces epithelial-to-mesenchymal transition and contributes to occurrence of esophageal cancer 39, 40. The mRNA and methylation changes may contribute to the more aggressive phenotype of radioresistant ESCC cells.…”

The long noncoding RNA H19 promotes cell proliferation via E2F-1 in pancreatic ductal adenocarcinoma

“…[10][11][12][13] In contrast, overexpression of H19 has been documented in breast cancer, bladder cancer, gastric cancer, colon cancer, esophageal cancer, lung cancer, osteosarcoma, epithelial ovarian cancer and cervical cancer. 8,[14][15][16][17][18][19][20][21] Aberrant expression of H19 in these tumors is related to increased cell proliferation and invasion and reduced apoptosis.…”