Role of LncRNAs in the Epithelial-Mesenchymal Transition in Hepatocellular Carcinoma

Abstract

Hepatocellular carcinoma (HCC) is a type of primary liver cancer with a high incidence and mortality rate. HCC develops insidiously, and most newly diagnosed cases are in the middle and advanced stages. The epithelial-mesenchymal transition (EMT) is a vital mechanism underlying metastasis in patients with advanced HCC. EMT is a multistep and complex procedure. The promotion and inhibition of EMT directly affect the migration and invasion of HCC. LncRNAs are involved in the epigenetic modification of genes, regulation of gene transcription, and posttranslational modification of proteins. LncRNAs also play important roles in regulating EMT progression in HCC and are promising biomarkers and therapeutic targets. This review focused on summarizing the mechanism by which lncRNAs regulate EMT in HCC. In particular, lncRNAs were reported to primarily act as RNA sponges, and the regulation of EMT involves major signaling pathways. Finally, we reviewed the mechanisms by which lncRNAs are involved in drug resistance and discussed the clinical prospects and potential challenges of utilizing lncRNAs to treat HCC.

Non-coding RNAs in hepatocellular carcinoma: Insights into regulatory mechanisms, clinical significance, and therapeutic potential

“…EMT is indispensable at all life stages from embryonic development to death, and it is essential for the acquisition of the invasive and metastatic characteristics of malignant tumors. Featured with reversibility, plasticity, and heterogeneity, EMT can alter multiple phenotypic changes including the loss of cell polarity, dissolution of intracellular junctions, and basement membrane detachment ( 9 , 10 ). Epithelioid cell markers, such as β-catenin, E-cadherin, ZO-1, and claudin-1, were negatively correlated with the EMT process, while mesenchymal-like cell markers, such as Snail, twist, vimentin, N-cadherin, ZEB, and α-SMA, were positively correlated with the EMT process.…”

“…Angiogenesis not only delivers oxygen and nutrients to the growing tumor but also transports tumor cells to the metastatic site ( 8 ). Epithelial-mesenchymal transition (EMT) is a complex phenotypic event that directly affects changes in the characteristic features of HCC, such as occurrence, migration, invasion, metastasis, and even drug resistance ( 9 , 10 ). Following primary tumor growth, angiogenesis and EMT, tumors are more prone to invasion and metastasis, which plays a key role in limiting patient outcomes overall.…”

Regulation of epithelial-mesenchymal transition by protein lysine acetylation

“…Moreover, when epithelial cells undergo EMT, the expression of epithelioid markers, including E-cadherin, claudin-1, and EpCAM, is repressed. In contrast, mesenchymal markers, such as N-cadherin, αSMA, and vimentin, are upregulated during this transition [4][5][6][7]. In addition, current evidence shows that EMT is a stepwise complex process with distinct intermediate states rather than functioning in a binary manner [8,9].…”

Immune landscape of a prognostic immunogenic cell death (ICD)-related long noncoding RNAs (lncRNAs) signature in colon adenocarcinoma (COAD)

“…Long noncoding RNAs (LncRNA) have been generally accepted as promising biomarkers in the diagnosis and prognosis of cancer patients. LncRNAs regulated multiple cellular process, including cell proliferation, apoptosis, cell cycle, migration and invasion [14,15]. The relationships between lncRNA and ICD have not been well elucidated.…”