Noncoding RNAs in cancer therapy resistance and targeted drug development

Abstract

Noncoding RNAs (ncRNAs) represent a large segment of the human transcriptome and have been shown to play important roles in cellular physiology and disease pathogenesis. Increasing evidence on the functional roles of ncRNAs in cancer progression emphasizes the potential of ncRNAs for cancer treatment. Here, we summarize the roles of ncRNAs in disease relapse and resistance to current standard chemotherapy and radiotherapy; the current research progress on ncRNAs for clinical and/or potential translational applications, including the identification of ncRNAs as therapeutic targets; therapeutic approaches for ncRNA targeting; and ncRNA delivery strategies in potential clinical translation. Several ongoing clinical trials of novel RNA-based therapeutics were also emphasized. Finally, we discussed the perspectives and obstacles to different target combinations, delivery strategies, and system designs for ncRNA application. The next approved nucleic acid drug to treat cancer patients may realistically be on the horizon.

LINC00511 contributes to glioblastoma tumorigenesis and epithelial‐mesenchymal transition via LINC00511/miR‐524‐5p/YB1/ZEB1 positive feedback loop

“…Studies have reported that the long non-coding RNA (lncRNA) RP11 promotes colorectal cancer cells dissemination by ZEB1 overexpression, whereas lncRNA HCCL5 could be activated by ZEB1 to promote hepatocellular carcinoma malignancy. 18,19 Among these, lncRNAs are a class of ncRNAs of more than 200 bp that have been demonstrated to be closely related to cancer progression, including tumorigenesis, 20 stemness, 21 apoptosis, 22 25 It has also been reported that LINC00511 promotes proliferation in pancreatic ductal adenocarcinoma, 26 ovarian cancer 27 and glioma. 16,17 Non-coding RNAs (ncRNAs) are transcribed genes that are not further translated into proteins and include lncRNAs, circular RNAs (circRNAs) and miRNAs, which perform vital roles in human cancers.…”

Low expression of lncRNA CTB-104H12.5 induces resistance to adriamycin in HER2 negative breast cancer by downregulating GAS7C

“…Several biomarkers have been reported to be able to predict the e cacy of anthracycline-based chemotherapy in breast cancer, for example, the expression levels of CREB3L1 in TNBC responsive to doxorubicin-based chemotherapy were signi cantly higher than that in resistant cancers [14], and loss of FKBP12 function in invasive breast cancers predicts poor prognosis and chemoresistance to doxorubicin [15] while HOXD3 overexpression enhances breast cancer cell drug resistance via integrin β3-mediated Wnt/β-catenin signaling [16]. Recently, increasing evidence has supported that ncRNAs also play an important role in drug resistance of breast cancer [17,18]. Among these ncRNAs, lncRNAs, as the promising molecular markers for forecasting drug resistance of breast cancer, are becoming new targets for treating breast cancer in the future.…”

NoncoRNA: a database of experimentally supported non-coding RNAs and drug targets in cancer

“…However, the mechanism of drug resistance to chemotherapeutic agents is not fully elucidated. Currently, more and more evidences have been proved that non-coding RNAs play critical roles in drug resistance [3][4][5][6]. ncRNAs including long non-coding RNAs (lncRNAs), microRNAs (miRNAs), circular RNAs (circRNAs), and PIWI-interacting RNAs (piRNAs) are suggested to be the potential promising therapeutic targets for overcoming drug resistance in the treatment of human cancers [7][8][9][10].…”