The Effect of LncRNA H19/miR-194-5p Axis on the Epithelial-Mesenchymal Transition of Colorectal Adenocarcinoma

Abstract

Background/Aims: Since the combined actions of lncRNAs and miRNAs have been considered to be involved in the occurrence and development of various neoplasms, the main purpose of this study was to discover whether and how lncRNA H19 and miR-194 influenced the epithelial-mesenchymal transition (EMT) process of colorectal adenocarcinoma (CRA). Methods: Totally 214 pairs of CRA and adjacent normal tissues were collected, and 5 human CRA cell lines (i.e. HCT116, HT-29, RKO SW280 and Lovo) were purchased. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was adopted to quantify the H19 and miR-194-5p expressions in cells and tissues. The expressions of FoxM1, E-cadherin, vimentin, N-cadherin were determined using western blot. On the side, si-H19, si-NC, miR-194-5p mimic, miR-194-5p inhibitor and negative control (NC) were transfected into CRA cell lines. Meanwhile, the invasive, migratory and proliferative conditions of the cells were assessed through transwell, wound healing and colony-forming experiments, with final verification of the relationship between H19 and miR-194-5p employing dual-luciferase reporter gene assay. Results: Highly-expressed H19, lowly-expressed miR-194-5p, low-grade differentiation and lymph node metastasis appeared as the independent predictors of unfavorable prognosis in CRA patients’ (all P< 0.05). It indicated that FoxM1 expression displayed positive correlations with H19 expression, yet negative associations with miR-194-5p expression within CRA tissues (P< 0.05). In addition, transfection of H19-siRNA and miR-145-5p mimic triggered a conspicuous increase in E-cadherin expression, as well as an evidently down-regulation in vimentin and N-cadherin expressions within HT29 and RKO cells (P< 0.05). On the other hand, the invasive and migratory capacities of CRA cells were significantly hindered (P< 0.05). Moreover, the luciferase reporter gene assay confirmed that H19 modified miR-194-5p expression through directly targeting at it (P< 0.05). Ultimately, FoxM1 could reverse the role of miR-194-5p in inhibiting invasion, migration and EMT of CRA cells (P< 0.05). Conclusion: LncRNA H19/miR-194/FoxM1 axis could serve as a profound target for the diagnosis and treatment of CRA.

Prognostic and clinicopathological significance of SNHG6 in human cancers: a meta-analysis

“…With the deepening of research, a wide range of cellular processes, such as alternative splicing control and translation, chemical RNA modification, pre-RNA processing and host mRNA stabilisation, have been demonstrated to be related to the dysregulation of lncRNAs [30,31]. Additionally, the interaction network of mRNAs and lncRNAs plays vital roles in the occurrence and recurrence of diverse cancers, and the regulatory mechanism may be linked to the competition in binding miRNA targets [32,33]. SNHG6, as a novel cancer-related lncRNA, is located at chromosome 8q13 and has an evident connection with the structural integrity of the translation initiation complex and ribosomes, and it has become a new frontier of research [34].…”

H19/miR-194/E2F3 regulating loop promotes gastric cancer growth and metastasis

“…H19 located on human chromosome 11p15.5. Studies have found that H19 overexpressed in various malignancies, which indicated that H19 overexpression could upregulate the proliferation of tumor cells and promote tumor cell migration and invasion [10,11].…”

Comprehensive Analysis of LncRNAs Role in Tumorigenesis of Colon Adenocarcinoma

“…Aberrant expression of lncRNAs has been welldocumented in different sorts of cancers [8]. Dysregulation of lncRNA HOTAIR, H19, MALAT1, SNHG7, GAS8-AS, and NEAT1 were extensively well-studied and have been demonstrated to contribute in tumorigenesis and poor prognosis [5,[8][9][10][11][12]. A mounting of investigations have shown that lncRNAs exert their function through competing for endogenous RNA (ceRNA) crosstalk [13].…”