Long Non-coding RNAs Involved in Resistance to Chemotherapy in Ovarian Cancer

Abstract

Ovarian cancer (OC) accounts for more than 150,000 deaths worldwide every year. Patients are often diagnosed at an advanced stage with metastatic dissemination. Although platinum-and taxane-based chemotherapies are effective treatment options, they are rarely curative and eventually, the disease will progress due to acquired resistance. Emerging evidence suggests a crucial role of long non-coding RNAs (lncRNAs) in the response to therapy in OC. Transcriptome profiling studies using high throughput approaches have identified differential expression patterns of lncRNAs associated with disease recurrence. Furthermore, several aberrantly expressed lncRNAs in resistant OC cells have been related to increased cell division, improved DNA repair, up-regulation of drug transporters or reduced susceptibility to apoptotic stimuli, supporting their involvement in acquired resistance. In this review, we will discuss the key aspects of lncRNAs associated with the development of resistance to platinum-and taxane-based chemotherapy in OC. The molecular landscape of OC will be introduced, to provide a background for understanding the role of lncRNAs in the acquisition of malignant properties. We will focus on the interplay between lncRNAs and molecular pathways affecting drug response to evaluate their impact on treatment resistance. Additionally, we will discuss the prospects of using lncRNAs as biomarkers or targets for precision medicine in OC. Although there is still plenty to learn about lncRNAs and technical challenges to be solved, the evidence of their involvement in OC and the development of acquired resistance are compelling and warrant further investigation for clinical applications.

Novel role of lncRNA CHRF in cisplatin resistance of ovarian cancer is mediated by miR-10b induced EMT and STAT3 signaling

“…The CHRF-miR-10b axis described by us in this study has never been reported, neither in OC nor in the cisplatin resistance, and this signifies the innovative findings from our study. lncRNAs are increasingly being recognized to be involved in progression of human cancers 10 and even in the cisplatin resistance 13,24 and our results provide more value to such progress in the field. In our present study, CHRF was chosen from a few shortlisted lncRNAs.…”

Long noncoding RNA PSMA3‑AS1 functions as a microRNA‑409‑3p sponge to promote the progression of non‑small cell lung carcinoma by targeting spindlin 1

“…The dysregulation of lncRNAs in various types of cancer is a growing concern among researchers (27,28). Emerging studies have revealed that several lncRNAs are aberrantly expressed in NSCLC, and they have been recognized to perform oncogenic or anti-oncogenic activities during NSCLC progression (16,29,30).…”

De Novo T790M Mutation in an L858R Epidermal Growth Factor Receptor Mutant-Associated Lung Adenocarcinoma

“…In all of these studies, the EGFR transgenic constructs were generated by cloning the hEGFR cDNA that encodes the mutant transgenes, which therefore lacked the genetic information from the non-coding regions of the hEGFR gene. An increasing amount of evidence suggests that the gene non-coding regions are involved in predisposition, progression, invasiveness, metastasis, and drug resistance of malignant tumors and that their activity correlates with patient survival [ 14 , 15 , 16 , 17 , 18 ]. To develop lung cancer mouse models that closest resemble the human disease, here we generated two transgenic mice each of them carrying a mutant transgene that contains the full-length of genomic hEGFR, and thereby the mutant transgenes have the complete coding and non-coding genetic information of the hEGFR gene.…”