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Review
. 2021 Jun 15;22(12):6374.
doi: 10.3390/ijms22126374.

The Role of lncRNAs in the Stem Phenotype of Pancreatic Ductal Adenocarcinoma

Jorge Melendez-Zajgla  1 , Vilma Maldonado  2
Affiliations
Review

The Role of lncRNAs in the Stem Phenotype of Pancreatic Ductal Adenocarcinoma

Jorge Melendez-Zajgla et al. Int J Mol Sci. .

Abstract

Pancreatic ductal adenocarcinoma is one of the deadliest tumors. This neoplasia is characterized by an important cellular and phenotypic heterogeneity. In particular, it has been shown that at least two subtypes can be found: basal-like, which presents stem-like properties, and classical. Cancer stem cells have been isolated and characterized from these tumors, showing their dependance on general and tissue-specific stem transcription factors and signaling pathways. Nevertheless, little is known about their tissue microenvironment and cell non-autonomous regulators, such as long-non-coding RNAs. (lncRNAs). In this review, we summarize the current knowledge about the positive and negative effects of lncRNAs in the stemness phenotype of pancreatic ductal adenocarcinoma cancer (PDAC).

Keywords: cancer stem cells; non-coding RNAs; tumor initiating cells.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
LncRNAs can be classified according to their function as: (A) sponges that act as competing endogenous molecules (ceRNAs) that interact with microRNAs and thus prevent them from interacting with their cognate mRNAs; (B) scaffold lncRNAs that act as adaptors to proteins; (C) enhancer or guide lncRNAs that stabilize chromosomal loops or recruit chromatin modifiers to DNA and (D) decoy lncRNAs, which act by sequestering proteins.
Figure 2
Figure 2
Several lncRNAs modulate the stem phenotype of pancreatic cancer stem cells by a direct effect on stem factors such as Nanog, Myc, Sox2, Oct4, etc. The most common molecular mechanism for this effect is acting as a competing endogenous RNA toward specific microRNAs. There have been hundreds of ceRNA reported examples since the initial description of this mechanism [118]. In this scenario, a microRNA that downregulates a group of mRNAs is “sequestered” by a pseudogene or a lncRNA in order to decrease its activity. This effect is thus a way to create a large-scale regulatory network.
Figure 3
Figure 3
Several lncRNAs modulate the stem phenotype of pancreatic cancer stem cells by an indirect effect on stem factors such as Nanog, Myc, Sox2, Oct4, etc. This indirect mechanism involves various signaling pathways previously associated with stemness. Nevertheless, most of final stages that connect these pathways with the stem factors are currently unknown.
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