Uncovering the roles of long non-coding RNAs in cancer stem cells

Abstract

Cancer has been a major public health problem that has threatened human life worldwide throughout history. The main causes that contribute to the poor prognosis of cancer are metastasis and recurrence. Cancer stem cells are a group of tumor cells that possess self-renewal and differentiation ability, which is a vital cause of cancer metastasis and recurrence. Long non-coding RNAs refer to a class of RNAs that are longer than 200 nt and have no potential to code proteins, some of which can be specifically expressed in different tissues and different tumors. Long non-coding RNAs have great biological significance in the occurrence and progression of cancers. However, how long non-coding RNAs interact with cancer stem cells and then affect cancer metastasis and recurrence is not yet clear. Therefore, this review aims to summarize recent studies that focus on how long non-coding RNAs impact tumor occurrence and progression by affecting cancer stem cell self-renewal and differentiation in liver cancer, prostate cancer, breast cancer, and glioma.

Keywords: Cancer stem cells; Long non-coding RNAs; Malignant transformation; Self-renewal; Tumor metastasis; Tumor recurrence.

Fig. 1

Four models of LncRNAs. Signal: LncRNAs can signal the space, time, and expression of gene transcription to modulate transcription factors and signaling pathways. LncRNAs directly bind to nucleic acid to inhibit the downstream molecule transcription named signal work model. Decoy: LncRNAs can bind and titrate away the protein or RNA target. LncRNAs combine with protein and then bind to nucleic acid to inhibit the downstream molecule transcription named decoy work model. Guide: LncRNAs can guide RNA-binding proteins to special target genes. Proteins guide LncRNA to bind to nucleic acid to inhibit the downstream molecule transcription named guide work model. Scaffold: LncRNAs can assemble different proteins to form complexes to initiate the special biological functions. Different proteins and LncRNAs combine together to bind to nucleic acid to inhibit the downstream molecule transcription named scaffold work model

Fig. 2

LncRNAs network in malignant transformation of HCC stem cells. Part 1: LncRNA CUDR impacts the malignant proliferation of liver CSCs trough different pathways. LncRNA CUDR act as oncogene by CUDR-HULC/CUDR-β-catenin signaling pathway; CUDR inhibits the methylation of gene promoter LncRNA H19 by combining with Cyclin-D to form the complex CUDR-CyclinD1, which upregulates the expression of LncRNA H19 and finally upregulates the expression of TERT and C-Myc to promote self-renewal and proliferation of HCC stem cells; LncRNA CUDR facilitate the interaction between SET1A and phosphorylated RB1 (pRB1) to be a complex contributing to the high level of H3K4 trimethylation, which took part in the malignant transformation of HCC stem cells via altering the length of telomere. Part 2: LncRNA HOTAIR can inhibit histone H3K36 trimethylation by suppressing SETD2. Then, to enhance the malignant proliferation of HCC stem cells via affecting the repair of aged histone, microsatellite stability, and cell cycle-related genes. Part 3: LncRNA TCF7 alter the expression of TCF7 by recruiting complex SWI/SNF to combine with TCF7 promoter region, which could activate WNT signaling pathways and accelerate self-renewal of HCC stem cells. Part 4: LncRNA DILC can inhibit liver CSCs’ self-renewal through the IL-6/STAT3 signaling pathway

Fig. 3

The roles of LncRNAs in malignant transformation of prostate CSCs. The PCR2-LncRNA HOTAIR complex which promotes by prostate tumor cells which treated with androgen-deprivation therapy (ADT) recruited mast cells to bind to androgen receptor (AR) gene to promote the invasion of prostate cancer through MMP9 and CD133⁺ stem/progenitor cells

Fig. 4

The roles of LncRNAs in the malignant transformation of breast CSCs. LncRNA HOTAIR affect the EMT phenomenon of breast cancer through HoxD10/miRNA-7/SETDB1/STAT3 pathway. At the same time, the secreted TGFβ could affect the expression of LncRNA HOTAIR. LncRNA 00617 and LncRNA SOX2OT contribute to EMT of breast cancer trough modulate SOX2. LncRNA ROR also could regulate the EMT of breast cancer

Fig. 5

The roles of LncRNAs in the malignant transformation of glioma stem cells. LncRNA uc.283-plus, LncRNA CRNDE, LncRNA-ROR, and LncRNA XIST impact glioma stem cell functions through different pathways. Knockdown of the LncRNA XIST in glioma cells could lead to miR-152 upregulation, which resulted in the inhibition of CSCs