scholarly journals Propagation and Maintenance of Cancer Stem Cells: A Major Influence of the Long Non-Coding RNA H19

Cells ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 2613
Author(s):  
Clément Lecerf ◽  
Evodie Peperstraete ◽  
Xuefen Le Bourhis ◽  
Eric Adriaenssens

Cancer stem cells (CSCs) represent a rare population of tumor cells that exhibit stem cell properties with the abilities of self-renewal and differentiation. These cells are now widely accepted to be responsible for tumor initiation, development, resistance to conventional therapies, and recurrence. Thus, a better understanding of the molecular mechanisms involved in the control of CSCs is essential to improve patient management in terms of diagnostics and therapies. CSCs are regulated by signals of the tumor microenvironment as well as intrinsic genetic and epigenetic modulators. H19, the first identified lncRNA is involved in the development and progression of many different cancer types. Recently, H19 has been demonstrated to be implicated in the regulation of CSCs in different types of cancers. The aim of this review is to provide an overview of the role and mechanisms of action of H19 in the regulation of CSCs. We summarize how H19 may regulate CSC division and cancer cell reprogramming, thus affecting metastasis and drug resistance. We also discuss the potential clinical implications of H19.

2021 ◽  
Author(s):  
Xiaobei Zhang ◽  
Meng Jin ◽  
Shiqi Liu ◽  
Mingde Zang ◽  
Lei Hu ◽  
...  

Abstract Background Cancer stem cells (CSCs) are proposed to be responsible for almost all malignant phenotypes (e.g. heterogeneity, uncontrolled growth, metastasis, recurrence, chemoresistance) of tumors. Long non-coding RNA WT1 antisense RNA (WT1-AS) has been found to be involved in the regulation of lung cancer cell stemness. However, the roles and molecular mechanisms of WT1-AS in the maintenance and development of gastric cancer stem cells (GSCs) have not been investigated. Methods mRNA and protein expression was measured by RT-qPCR and western blot. CCK8 and Soft agar colony formation assays were performed to assess cell viability and colony clone formation ability. Cell cycle and apoptosis were determined by flow cytometry analysis. Cell transwell and wound healing analyses were carried out to assess cell migration ability. In vitro angiogenesis and 3D spheroid cultures assays were also performed. Moreover, in vitro experiments were carried out to explore the function of WT1-AS on tumor growth, metastasis and cell stemness. The upstream transcription factors or downstream genes of WT1-AS were screened through Bioinformatics, dual-luciferase assays and RNA-sequencing (RNA-seq) technology. Results Our present study demonstrated that WT1-AS knockdown or wilms tumor 1 (WT1) overexpression improved GSC proliferative and migratory capacities, promoted GSC EMT, enhanced GSC stemness, inhibited GSC apoptosis, potentiated the resistance of GSCs to 5-FU and induced HUVEC angiogenesis in vitro. WT1-AS loss or WT1 increase facilitated the formation of in-vitro 3D GSC aggregates. WT1-AS ameliorated the malignant phenotypes of GSCs by down-regulating WT in vitro. Additionally, WT1-AS inhibited tumor growth and metastasis, and reduced tumor stemness in GSCs-derived xenografts (s.c., i.p., and i.v.) in vivo. Furthermore, XBP1 was identified as an upstream regulator of WT1-AS in GSCs. RNA-seq and RT-qPCR data suggested that PSPH, GSTO2, FYN, and PHGDH might be the downstream targets of WT1-AS in GSCs. Conclusions Our data demonstrated that WT1-AS weakened the stem-cell like behaviors and characteristics of GSCs in vitro and in vivo by down-regulating WT1. Also, some upstream regulators and downstream targets of WT1-AS were identified in GSCs. Investigations on the molecular mechanisms underlying the complex phenotypes of GSCs might contribute to the better management of headaches in cancers.


2018 ◽  
Vol 243 (13) ◽  
pp. 1074-1082 ◽  
Author(s):  
Xiujun Li ◽  
Jiali Wang ◽  
Yuchen Pan ◽  
Yujun Xu ◽  
Dan Liu ◽  
...  

Further studies on the molecular mechanisms of mesenchymal stem cells in the maintenance of growth and function are essential for their clinical application. Growing evidence has shown that long non-coding RNAs (lncRNAs) play an important role in the regulation of mesenchymal stem cells. Recently, it is reported that highly upregulated in liver cancer (HULC), with another lncRNA MALAT-1, accelerated liver cancer stem cell growth. The regulating role of MALAT-1 in mesenchymal stem cells has been investigated. However, the effects of HULC on the mesenchymal stem cells are unknown. In this study, we overexpressed HULC in mesenchymal stem cells derived from umbilical cord and analyzed the cell phenotypes, proliferation, apoptosis, migration, invasion and differentiation of mesenchymal stem cells. We found that overexpression of HULC significantly promotes cell proliferation through promoting cell division and inhibits cell apoptosis. HULC-overexpressed mesenchymal stem cells migrate and invade faster than control mesenchymal stem cells. HULC has no effect on phenotypes and differentiation of mesenchymal stem cells. Furthermore, we found that the expression of HULC in mesenchymal stem cells could be reduced by several inflammatory factors, including TNF-α, TGF-β1, and R848. Taken together, our data demonstrated that HULC has a vital role in the growth and function maintenance of mesenchymal stem cells without affecting differentiation. Impact statement Exploring the molecular mechanisms of growth and function in MSCs is the key to improve their clinical therapeutic effects. Currently, more and more evidence show that the long non-coding RNA (lncRNA) plays an important role in the growth, stemness and function of MSCs.Both HULC and MALAT1 are the earliest discovered LNCRNAs, which are closely related to tumor growth. All of them can promote the growth of liver cancer stem cells. Previously, we have studied the effects of MALAT1 on the growth and function of MSCs. In this study, we focused on the effects of HULC on MSCs. We elucidated the effects of HULC on the growth and differentiation of MSCs, and explored the relationship between inflammatory stimuli and HULC expression in MSCs. Our findings provide a new molecular target for the growth and clinical application of MSCs.


2019 ◽  
Vol 27 (1) ◽  
pp. 363-378 ◽  
Author(s):  
Dejan Vidovic ◽  
Thomas T. Huynh ◽  
Prathyusha Konda ◽  
Cheryl Dean ◽  
Brianne M. Cruickshank ◽  
...  

2016 ◽  
Vol 64 (6) ◽  
pp. 1283-1294 ◽  
Author(s):  
Xue Wang ◽  
Wen Sun ◽  
Weifeng Shen ◽  
Mingyang Xia ◽  
Cheng Chen ◽  
...  

2021 ◽  
Vol 27 (1) ◽  
Author(s):  
Senxiang Chen ◽  
Da Liu ◽  
Zimo Zhou ◽  
Sen Qin

Abstract Background Osteoporosis is a widespread and serious metabolic bone disease. At present, revealing the molecular mechanisms of osteoporosis and developing effective prevention and treatment methods are of great significance to health worldwide. LncRNA is a non-coding RNA peptide chain with more than 200 nucleotides. Researchers have identified many lncRNAs implicated in the development of diseases and lncRNA H19 is an example. Results A large amount of evidence supports the fact that long non-coding RNA (lncRNA) genes, such as H19, have multiple, far-reaching effects on various biological functions. It has been found that lncRNA H19 has a role in the regulation of different types of cells in the body including the osteoblasts, osteocytes, and osteoclasts found in bones. Therefore, it can be postulated that lncRNA H19 affects the incidence and development of osteoporosis. Conclusion The prospect of targeting lncRNA H19 in the treatment of osteoporosis is promising because of the effects that lncRNA H19 has on the process of osteogenic differentiation. In this review, we summarize the molecular pathways and mechanisms of lncRNA H19 in the pathogenesis of osteoporosis and summarize the research progress of targeting H19 as a treatment option. Research is emerging that explores more effective treatment possibilities for bone metabolism diseases using molecular targets.


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