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Review
. 2022 Jul 8;23(14):7594.
doi: 10.3390/ijms23147594.

MicroRNAs as Predictors of Lung-Cancer Resistance and Sensitivity to Cisplatin

Maria Konoshenko  1   2 , Yuriy Lansukhay  2 , Sergey Krasilnikov  2 , Pavel Laktionov  1   2
Affiliations
Review

MicroRNAs as Predictors of Lung-Cancer Resistance and Sensitivity to Cisplatin

Maria Konoshenko et al. Int J Mol Sci. .

Abstract

Background: Platinum-based chemotherapy, cisplatin (DDP) specifically, is the main strategy for treating lung cancer (LC). However, currently, there is a lack of predictive drug-resistance markers, and there is increased interest in the development of a reliable and sensitive panels of markers for DDP chemotherapy-effectiveness prediction. MicroRNAs represent a perspective pool of markers for chemotherapy effectiveness.

Objectives: Data on miRNAs associated with LC DDP chemotherapy response are summarized and analyzed.

Materials and methods: A comprehensive review of the data in the literature and an analysis of bioinformatics resources were performed. The gene targets of miRNAs, as well as their reciprocal relationships with miRNAs, were studied using several databases.

Results and discussion: The complex analysis of bioinformatics resources and the literature indicated that the expressions of 12 miRNAs have a high predictive potential for LC DDP chemotherapy responses. The obtained information was discussed from the point of view of the main mechanisms of LC chemoresistance.

Conclusions: An overview of the published data and bioinformatics resources, with respect to the predictive microRNA markers of chemotherapy response, is presented in this review. The selected microRNAs and gene panel have a high potential for predicting LC DDP sensitiveness or DDP resistance as well as for the development of a DDP co-therapy.

Keywords: DDP; chemoresistance; chemosensitivity; chemotherapy; cisplatin; lung cancer; microRNA; non-small cell lung cancer; therapeutic effectiveness markers.

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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
MicroRNAs and target genes implicated in LC DDP resistance via autophagy. Downregulation is shown by red arrows, and upregulation is shown by blue arrows. Overexpressed miRNAs and genes associated with DDP resistance (blue) and DDP sensitivity (red).
Figure 2
Figure 2
MicroRNAs and target genes implicated in LC DDP resistance via EMT. Downregulation is shown by red arrows and upregulation is shown by blue arrows. Overexpressed miRNAs and genes associated with DDP resistance (blue) and DDP sensitivity (red).
Figure 3
Figure 3
MicroRNAs inhibiting drug uptake or enhancing drug efflux and drug detoxification in DDP-resistant tumors. Downregulation is shown by red arrows, and upregulation is shown by blue arrows. MicroRNAs and genes associated with DDP resistance (blue) and DDP sensitivity (red).
Figure 4
Figure 4
Cell-cycle regulation by miRNAs and target genes in LC-DDP-resistant tumors. Downregulation is shown by red arrows, and upregulation is shown by blue arrows. MicroRNAs and genes associated with DDP resistance (blue) and DDP sensitivity (red).
Figure 5
Figure 5
MicroRNAs and target genes regulating apoptosis in LC-DDP-resistant cells. Downregulation is shown by red arrows, and upregulation is shown by blue arrows. MicroRNAs and genes associated with DDP resistance (blue) and DDP sensitivity (red) are shown.
Figure 6
Figure 6
MicroRNA involvement in DDP-resistance development through EMT, drug transportation, apoptosis, cell cycle, and autophagy regulation. MicroRNAs, in which low expression is associated with DDP resistance development (red) and miRNAs, in which high expression is associated with DDP resistance development (blue).
Figure 7
Figure 7
The interactions of proteins coded by genes that are regulated by miRNAs, which are the most valid as potential markers of DDP response and involved in lung-cancer regulation (STRING Database). Proteins involved in cellular response to DNA-damage stimulus (light blue); proteins involved in regulation of autophagy (red); proteins involved in stem-cell differentiation (green); proteins involved in regulation of epithelial-cell proliferation (dark green); proteins involved in cell-cycle regulation (blue); proteins involved in platinum drug resistance (yellow); proteins involved in apoptosis (pink).
Figure 8
Figure 8
MicroRNAs and genes involved in DDP response, with the greatest number of interactions according to Diana and Targetscan databases. Red arrows represent downregulation, and blue arrows represent upregulation.
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