LncRNAs in Ovarian Cancer Progression, Metastasis, and Main Pathways: ceRNA and Alternative Mechanisms

Chi²,

et al. 2021

Oncol Lett

USP30 antisense RNA 1 (USP30-AS1) has been studied in bladder urothelial carcinoma. However, the detailed role of USP30-AS1 in cervical cancer remains to be elucidated. Therefore, the present study determined whether USP30-AS1 is implicated in cervical cancer malignancy, and investigated relevant molecular mechanisms. USP30-AS1 expression was measured via reverse transcription-quantitative PCR. Functional experiments, including the Cell Counting Kit-8 assay, flow cytometry, Transwell migration and invasion assays, and mouse tumour model, were performed in order to elucidate the roles of USP30-AS1. The target of USP30-AS1 was predicted using bioinformatics analysis, which was further verified via RNA immunoprecipitation and luciferase reporter assays. Herein, USP30-AS1 overexpression was detected in cervical cancer sample data from The Cancer Genome Atlas and our cohort. Patients with cervical cancer expressing high levels of USP30-AS1 exhibited shorter overall survival than those with low USP30-AS1 expression. In vitro and in vivo experiments revealed that USP30-AS1 interference promoted cell apoptosis; restrained cell proliferation, migration and invasion in vitro, and hindered tumour growth in vivo. Mechanistically, USP30-AS1 competed for microRNA-299-3p (miR-299-3p) in cervical cancer and lowered the regulatory actions of miR-299-3p on protein tyrosine phosphatase type IVA (PTP4A1), resulting in PTP4A1 overexpression. Furthermore, rescue experiments confirmed that miR-299-3p interventions or exogenous PTP4A1 could counteract the cancer-inhibiting actions of USP30-AS1 silencing on cervical cancer cells. In conclusion, the miR-299-3p/PTP4A1 axis is the downstream effector of USP30-AS1 in cervical cancer, forming the USP30-AS1/miR-299-3p/PTP4A1 pathway. This newly identified competing endogenous RNA pathway may offer a novel theoretical and experimental basis for developing promising new strategies for the targeted therapy of cervical cancer.

Section: Discussionmentioning

confidence: 99%

Long non‑coding RNA USP30‑AS1 aggravates the malignant progression of cervical cancer by sequestering microRNA‑299‑3p and thereby overexpressing PTP4A1

Chi²,

et al. 2021

Oncol Lett

“…The important roles of lncRNAs in regulating physiological and pathological behaviours are achieved through various mechanisms. The lncRNA-mediated ceRNA theory is a classic mechanism that explains the mechanism of lncRNA action in EOC [12]. Cytoplasmic lncRNAs can act as endogenous molecular sponges to sequester certain miRNAs and indirectly modulate gene expression by protecting mRNAs from miRNA-induced mRNA deregulation or translation inhibition [33].…”

Section: Discussionmentioning

confidence: 99%

“…Functionally, lncRNAs are con rmed to be crucial modulators of diverse physiological and pathological processes, especially during tumorigenesis and cancer progression [10]. An increasing amount of evidence has shown that an imbalance in lncRNA expression is closely correlated with the progression of EOC [11][12][13]. The dysregulation of lncRNAs has been clearly shown to exert cancer-inhibiting or cancer-facilitating effects and to contribute to the control of multiple aggressive properties of EOC [14][15][16].…”

Section: Introductionmentioning

confidence: 99%

Silencing of Long Noncoding RNA LINC01132 Alleviates the Oncogenicity of Epithelial Ovarian Cancer by Regulating the microRNA-431-5p/SOX9 Axis

Zhu

Xiao

2021

Preprint

Background: To date, long intergenic nonprotein coding RNA 1132 (LINC01132) expression in epithelial ovarian cancer (EOC) and the underlying mechanisms have not been explored. In this study, we measured LINC01132 expression in EOC and assessed the effects of LINC01132 on the malignant behaviours of EOC cells in vitro and in vivo. Additionally, mechanistic studies were performed to elucidate the molecular events that occurred downstream of LINC01132 in EOC cells. Methods: Reverse-transcription quantitative PCR (RT-qPCR) was utilized to verify LINC01132 expression in EOC. The effects of LINC01132 on the malignant behaviours of EOC cells were determined using a Cell Counting Kit-8 assay, flow cytometry analysis, cell migration and invasion assays and a tumour xenograft model. The targeting interaction among LINC01132, microRNA-431-5p (miR-431-5p) and SRY-Box 9 (SOX9) was verified by RNA immunoprecipitation and luciferase reporter assays. Results: LINC01132 was overexpressed in EOC and was obviously associated with poor patient prognosis. Functionally, cell experiments revealed that LINC01132 depletion could inhibit EOC cell proliferation, migration and invasion and promote cell apoptosis in vitro. Additionally, loss of LINC01132 attenuated tumour growth in vivo. Mechanistically, LINC01132 acted as a competing endogenous RNA by sequestering miR-431-5p and thereby increasing SOX9 expression in EOC cells, forming a LINC01132/miR-431-5p/SOX9 axis. In rescue experiments, miR-431-5p inhibition or SOX9 re-expression eliminated the inhibitory effects of LINC01132 silencing on the pathological behaviours of EOC cells. Conclusions: Generally, LINC01132 exhibited oncogenic activities in EOC cells in vitro and in vivo by regulating the outcome of the miR-431-5p/SOX9 axis, providing an effective target for EOC diagnosis, therapy and prognosis evaluation.

“…Another epigenetic target to be considered is EZH2 because of its association with numerous ncRNAs. Indeed, EZH2 inhibition showed therapeutic efficacy against ovarian, colon and bladder cancers [175,250]. Tazemetostat, an EZH2 inhibitor, showed encouraging results in a phase 1 clinical trial for treating relapsed or refractory B-cell non-Hodgkin's lymphoma [251].…”

Section: Use Of Ncrnas In Clinical Therapymentioning

confidence: 99%

Non-Coding RNAs as Mediators of Epigenetic Changes in Malignancies

Kumar

Gonzalez

Rameshwar

et al. 2020

Cancers

Non-coding RNAs (ncRNAs) are untranslated RNA molecules that regulate gene expressions. NcRNAs include small nuclear RNAs (snRNAs), small nucleolar RNAs (snoRNAs), ribosomal RNAs (rRNAs), transfer RNAs (tRNAs), circular RNAs (cRNAs) and piwi-interacting RNAs (piRNAs). This review focuses on two types of ncRNAs: microRNAs (miRNAs) or short interfering RNAs (siRNAs) and long non-coding RNAs (lncRNAs). We highlight the mechanisms by which miRNAs and lncRNAs impact the epigenome in the context of cancer. Both miRNAs and lncRNAs have the ability to interact with numerous epigenetic modifiers and transcription factors to influence gene expression. The aberrant expression of these ncRNAs is associated with the development and progression of tumors. The primary reason for their deregulated expression can be attributed to epigenetic alterations. Epigenetic alterations can cause the misregulation of ncRNAs. The experimental evidence indicated that most abnormally expressed ncRNAs impact cellular proliferation and apoptotic pathways, and such changes are cancer-dependent. In vitro and in vivo experiments show that, depending on the cancer type, either the upregulation or downregulation of ncRNAs can prevent the proliferation and progression of cancer. Therefore, a better understanding on how ncRNAs impact tumorigenesis could serve to develop new therapeutic treatments. Here, we review the involvement of ncRNAs in cancer epigenetics and highlight their use in clinical therapy.