The Role of Autophagy and lncRNAs in the Maintenance of Cancer Stem Cells

Abstract

Cancer stem cells (CSCs) possess properties such as self-renewal, resistance to apoptotic cues, quiescence, and DNA-damage repair capacity. Moreover, CSCs strongly influence the tumour microenvironment (TME) and may account for cancer progression, recurrence, and relapse. CSCs represent a distinct subpopulation in tumours and the detection, characterisation, and understanding of the regulatory landscape and cellular processes that govern their maintenance may pave the way to improving prognosis, selective targeted therapy, and therapy outcomes. In this review, we have discussed the characteristics of CSCs identified in various cancer types and the role of autophagy and long noncoding RNAs (lncRNAs) in maintaining the homeostasis of CSCs. Further, we have discussed methods to detect CSCs and strategies for treatment and relapse, taking into account the requirement to inhibit CSC growth and survival within the complex backdrop of cellular processes, microenvironmental interactions, and regulatory networks associated with cancer. Finally, we critique the computationally reinforced triangle of factors inclusive of CSC properties, the process of autophagy, and lncRNA and their associated networks with respect to hypoxia, epithelial-to-mesenchymal transition (EMT), and signalling pathways.

Deep analysis of neuroblastoma core regulatory circuitries using online databases and integrated bioinformatics shows their pan-cancer roles as prognostic predictors

“…Hence, the positive association of EGR3 gene expression with CAFs in these cancers suggests the contribution of this gene to promoting the immunosuppressive roles of CAFs, while negative correlations obtained for Tregs in DLCBCL would suggest the reverse. Moreover, different components of the TME, including tumour-associated macrophages (TAMs), induce EMT and cancer cell migration, while EMT, chiefly triggered by hypoxia can activate stemness factors [ 33 ]. Hence, we sought to understand the influence of these TFs on the occurrence of EMT and the expression of stemness factors.…”

“…Given the link between MES and ADRN TFs and cancer cell migration and the activation of stemness factors [ 33 , 57 ], we used the TIMER2 gene correlation module to establish such associations, detailed further in Additional file 1 : Materials S5. For example, a positive correlation with all markers tested including CD44, CDH1, CDH2, FN1, FOXC2, NANOG, SOX2, TWIST1, and VIM was observed with the following MES and ADRN TFs: SMAD3, CBFB, ZFP36L, KLF7, DACH1, and SATB1 in liver hepatocellular carcinoma (LIHC).…”

“…Notably, similar associations between MES and ADRN TFs with the infiltration of cancer-associated fibroblasts (CAFs) of the TME implicate these TFs in pro-tumourigenic remodelling of the TME in cancers [ 28 – 31 ]. Furthermore, tightly associated with these events are epithelial to mesenchymal transition (EMT) and cancer stemness markers, including CD44, CDH1, CDH2, FN1, FOXC2, NANOG, SOX2, TWIST1, and VIM that are triggered by hypoxia in the TME [ 32 , 33 ]. Given this background, we were intrigued to conduct a comprehensive pan-cancer assessment of the association of these TFs with the infiltration of tumour-associated immune and stromal cells in the TME.…”

Capsaicin inhibits the stemness of anaplastic thyroid carcinoma cells by triggering autophagy‐lysosome mediated OCT4A degradation

“…It is widely acknowledged that tumor stem cell-like cells within ATC cells are responsible for the dismal outcome of ATC (Giuffrida & Rogers, 2010). Autophagy also was a vital role in the pluripotency of cancer stem cell (CSC) (Jahangiri et al, 2021). Sphere formation was widely used to characterize the CSC properties (Weiswald, Bellet, & Dangles-Marie, 2015).…”

Dormancy in Breast Cancer, the Role of Autophagy, lncRNAs, miRNAs and Exosomes

“…The cell population intended throughout this review, however, encapsulates the quiescent dormant tumour cells described above, referred to herein as "dormant cells" that may not respond to therapy and subsequently lead to metastasis and disease recurrence [18][19][20][21][22][23][24]. In addition, the literature reports overlapping characteristics of cancer stem cells (CSCs) and quiescent dormant tumour cells, for instance, the ability to resist therapy, although in our opinion, cancer persister cells may be a better representative of the cell population resisting therapy, while CSCs may represent the cell population propagating an existing tumour [25]. Nonetheless, CSCs may be viewed as dormancy-competent tumour repopulating cells [26,27].…”