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. 2021 Mar 9;13(5):1168. doi: 10.3390/cancers13051168

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© 2021 by the authors.

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).

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miRNA-lncRNAs regulatory loops determine cisplatin resistance in cervical cancer. In cisplatin-sensitive cells (blue rectangles) GAS5 or CASC2 lncRNAs sponge miR-21, thus PTEN dephosphorylates PIP3 into PI2, preventing AKT pathway activation, resulting in reduced proliferation, drug resistance, and increased cell apoptosis (A). In resistant cells (red rectangle), the downregulation of GAS5 and CASC2 cause the PTEN inhibition by miR-21 determining the PI3K/AKT pathway activation (B). MiR-21 can also contribute to the repression of the two lncRNAs (A,B). In cisplatin-resistant cells (red rectangle), the sponging of miR-134-5p by NCK1-AS1 leads to MSH2, ABCB1, and Bcl-2 up-regulation determining drug resistance and cell survival (D). In cisplatin-sensitive cells (blue rectangle), the downregulation of the lncRNA NCK1-AS1 determines the inhibition of MSH2 by miR-134-5p, associated with a decrease of ABCB1 and Bcl-2 to promote cisplatin-induced cell death (C).

miRNA-lncRNAs regulatory loops determine cisplatin resistance in cervical cancer. In cisplatin-sensitive cells (blue rectangles) GAS5 or CASC2 lncRNAs sponge miR-21, thus PTEN dephosphorylates PIP3 into PI2, preventing AKT pathway activation, resulting in reduced proliferation, drug resistance, and increased cell apoptosis (A). In resistant cells (red rectangle), the downregulation of GAS5 and CASC2 cause the PTEN inhibition by miR-21 determining the PI3K/AKT pathway activation (B). MiR-21 can also contribute to the repression of the two lncRNAs (A,B). In cisplatin-resistant cells (red rectangle), the sponging of miR-134-5p by NCK1-AS1 leads to MSH2, ABCB1, and Bcl-2 up-regulation determining drug resistance and cell survival (D). In cisplatin-sensitive cells (blue rectangle), the downregulation of the lncRNA NCK1-AS1 determines the inhibition of MSH2 by miR-134-5p, associated with a decrease of ABCB1 and Bcl-2 to promote cisplatin-induced cell death (C).