Research Progress on Regulating LncRNAs of Hepatocellular Carcinoma Stem Cells

Abstract

Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies around the world. The self-renewal, proliferation, differentiation, and tumorigenic potential of liver cancer stem cells (LCSCs) may account for the high recurrence rate and the refractory feature of HCC. Despite extensive researches, the underlying regulatory mechanism of LCSCs has not been fully disclosed. Long nonprotein coding RNAs (lncRNAs) may exert an essential role in regulating various biological functions of LCSCs, such as maintaining the stemness of cancer stem cells (CSCs) and promoting tumor development. Therefore, it is highly critical to determine which lncRNAs can control LCSCs functions and understand how LCSCs are regulated by lncRNAs. Herein, we summarized lncRNAs and the main signaling pathways involved in the regulation of LCSCs found in recent years. Moreover, we shed light on the existence of the network system of lncRNAs and LCSCs, which may provide valuable clues on targeting LCSCs.

Function of the Long Noncoding RNAs in Hepatocellular Carcinoma: Classification, Molecular Mechanisms, and Significant Therapeutic Potentials

“…Although ncRNAs are not translated into proteins, they play important roles in the physiological functions of organisms [ 69 , 83 ]. In particular, lncRNAs are essential controllers of chromatin dynamics, growth, differentiation, and gene development [ 20 , 84 ]. At present, with the advancement of high-throughput sequencing and DNA tiling array technology, a number of investigations are concentrating on ncRNAs [ 85 , 86 , 87 ].…”

“…In turn, miRNAs may directly interact with lncRNAs to silence their expressions. Various lncRNAs are difficult to classify in specific classifications [ 20 , 28 , 49 , 98 , 99 ].…”

“…Hepatocellular carcinoma (HCC), a severe specific type of primary liver cancer [ 15 ], accounts for 75–85% of cases of death [ 16 , 17 , 18 , 19 , 20 ]. The low survival rate of HCC is due to asymptomatic initiation in premature stages and loss of optimum treatment period after diagnosis in middle or late stages [ 17 ].…”

“…The long noncoding RNAs (lncRNAs) are mainly categorized according to their positional relationship with adjacent coding genes [ 59 ]. Several reports have been published in the scientific literature, highlighting a potential role for lncRNAs in tissue pathophysiology and development [ 20 , 49 , 60 , 61 ]. Evidence has shown that lncRNAs are mostly dysregulated as tumor suppressors in various cancers [ 20 , 62 ], and many lncRNAs are intricately linked to the progression of cancer, including HCC [ 25 , 63 , 64 , 65 , 66 , 67 ], signifying that lncRNAs are potential therapeutic targets in HCC [ 68 ].…”

Long non‐coding RNA DUXAP9 promotes hepatocellular carcinoma cell stemness via directly interacting with sox9

“…Recent studies have demonstrated that lncRNA critically functions in HCC cell stemness 8,9 . LncRNA DUXAP9 (Double Homeobox A Pseudogene 9) was firstly reported to be highly expressed in HCC tissues and correlated with a poor prognosis of HCC patients 10 .…”