The lncRNA H19 promotes epithelial to mesenchymal transition by functioning as miRNA sponges in colorectal cancer

Abstract

Recently, the long non-coding RNA (lncRNA) H19 has been identified as an oncogenic gene in multiple cancer types and elevated expression of H19 was tightly linked to tumorigenesis and cancer progression. However, the molecular basis for this observation has not been characterized in colorectal cancer (CRC) especially during epithelial to mesenchymal transition (EMT) progression. In our studies, H19 was characterized as a novel regulator of EMT in CRC. We found that H19 was highly expressed in mesenchymal-like cancer cells and primary CRC tissues. Stable expression of H19 significantly promotes EMT progression and accelerates in vivo and in vitro tumor growth. Furthermore, by using bioinformatics study and RNA immunoprecipitation combined with luciferase reporter assays, we demonstrated that H19 functioned as a competing endogenous RNA (ceRNA) for miR-138 and miR-200a, antagonized their functions and led to the de-repression of their endogenous targets Vimentin, ZEB1, and ZEB2, all of which were core marker genes for mesenchymal cells. Taken together, these observations imply that the lncRNA H19 modulated the expression of multiple genes involved in EMT by acting as a competing endogenous RNA, which may build up the missing link between the regulatory miRNA network and EMT progression.

miR‐193b availability is antagonized by LncRNA‐SNHG7 for FAIM2‐induced tumour progression in non‐small cell lung cancer

“…4 Zhuang et al 24 cells. 28 In this study, SNHG7 modulated miR-193b availability by acting as a molecular sponge, which down-regulated the miR-193b levels to enhance its target gene FAIM2-induced tumour survival,…”

LncRNA UCA1 promotes the invasion and EMT of bladder cancer cells by regulating the miR‑143/HMGB1 pathway

“…LncRNAs can also function as a competing endogenous RNA to sponge microRNAs (12)(13)(14). For example, the lncRNA H19 promotes EMT by functioning as a miRNA sponge to miR-138 and miR-200a in colorectal cancer (15). Therefore, by interacting with specific miRNAs, lncRNAs can play an important role in cancer development and progression.…”

Systemic analysis of lncRNA and miRNA expression profiles with associated ceRNA network in glioblastoma

“…While, recently studies identified several lncRNAs as valuable diagnosis and prognosis biomarkers in cancers and other types of complex diseases, such as lncRNA-p53, H19, MALAT1 [16,32,33]. In this study, besides differential expression analysis of lncRNA, miRNA and mRNA, we also drew our attention to the prognosis significance of DEL.…”

“…And thus, the three types of RNA form the lncRNA-miRNA-m RNA ceRNA network, which should play important roles in many types of diseases. Liang and collages [16] illustrated that lncRNA H19 promotes epithelial to mesenchymal (ETM) transition by acting as miRNAs sponge in colorectal cancer. Endogenous miRNA sponge lincRNA-RoR regulates Oct4, Nanog, and Sox2 in human embryonic stem cell self-renewal [17].…”