LncRNA LOC102724169 plus cisplatin exhibit the synergistic anti-tumor effect in ovarian cancer with chronic stress

Xiaofang Zhou,Mu Liu,Guanming Deng,Le Chen,Lijuan Sun,Yun Zhang,Chenhui Luo,Jie Tang

doi:10.1016/j.omtn.2021.03.001

Abstract

Chronic stress has been proven to accelerate the development and progression of ovarian cancer, but the underlying molecular mechanisms have not been fully elucidated. In a combination survey of ovarian cancer with chronic stress (OCCS) mouse models and high-throughput sequencing, a key lncRNA named LOC102724169 on chromosome 6q27 has been identified, which functions as a dominant tumor suppressor in OCCS. Transcriptionally regulated by CCAAT enhancer binding protein (CEBP) beta (CEBPB), LOC102724169 shows low expression and correlates with poor progression-free survival (PFS) in OCCS patients. LOC102724169 is an instructive molecular inhibitor of malignancy of ovarian cancer cells, which is necessary to improve the curative effect of cisplatin therapy on ovarian cancer. This function stems from the inactivation of molecules in phosphatidylinositol 3-kinase (PI3K)/AKT signaling, repressing MYB expression and retaining the responsiveness of cancer cells to cisplatin. These findings provide a mechanistic understanding of the synergistic anti-tumor purpose of LOC102724169 as a bona fide tumor suppressor, enhancing the therapeutic effect of cisplatin. The new regulatory model of “lncRNA-MYB” provides new perspectives for LOC102724169 as a chronic stress-related molecule and also provides mechanistic insight into exploring the cancer-promoting mechanism of MYB in OCCS, which may be a promising therapeutic strategy for ovarian cancer.

Highlights

Epithelial ovarian cancer (EOC) is one of the most lethal gynecological cancers globally
These differentially expressed genes were enriched in Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways such as apoptosis, ABC transporters, the phosphatidylinositol 3-kinase (PI3K)/AKT pathway, and the mitogen-activated protein kinase (MAPK) pathway, which are linked to either multi-drug resistance or oncogenesis (Figure 1E)
We randomly validated several genes such as IGSF10, TGFBR3, and others (Table S1) from 181 mRNAs and Long non-coding RNAs (lncRNAs) mentioned above in the other mouse tumor tissues (Figure 1G), and we found that the result was consistent with what we observed in the highthroughput sequencing (Figure 1D)

Summary

Introduction

Epithelial ovarian cancer (EOC) is one of the most lethal gynecological cancers globally. Better prognosis has been observed in breast cancer and malignant melanoma using them.[12,13] other studies show that taking beta blockers does not significantly prolong survival in ovarian cancer patients.[14,15,16] This suggests that some other major underlying mechanisms are still unclear in ovarian cancer with chronic stress (OCCS)

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Conclusion