Abstract

As one of the main gynecological cancers, ovarian cancer (OC) has an unfavourable outcomes owing to its high recurrence and metastasis rate. Our previous studies have revealed that LINC01296 functions as an oncogene in OC, but the underlying mechanism has not been explored. The aim of this paper was to further investigate that how LINC01296 plays a role in OC. Through online software prediction, miR-29c-3p has been discriminated as the target miRNA of LINC01296 for further research, and subsequent luciferase assay confirmed bioinformatics prediction. Then the data obtained from the two databases (GSE119055 and GSE83693) were analyzed by GEO2R for differential gene analysis. The results indicated that the miR-29c-3p was lowly expressed in OC tissues than that in normal ovarian tissues, and its expression in recurrent OC tissues was lower than that in primary OC tissues. Simultaneously, Kaplan-Meier survival analysis illustrated that the lower expression of miR-29c-3p was interrelated to unfavourable outcomes of OC. Further, the qRT-PCR data revealed that the miR-29c-3p expression in OC cell lines (SKOV-3 and OVCAR-3) was markedly declined than that in normal control cells (IOSE80). Subsequently, the functional experiments, such as CCK8, colony formation and Transwell assays, prompted that inhibition of miR-29c-3p can obviously increase the proliferation, invasion and migration of OVCAR3 and SKOV3 cells compared with control group, while downregulation of LINC01296 showed an opposite result. It is worth noting that downregulation of LINC01296 can reverse the effect of miR-29c-3p suppression on OC cells. Finally, we detected the changes of EMT-related proteins by western blot experiment, and reached a similar conclusion that knockdown of LINC01296 reversed the EMT caused by miR-29c-3p inhibition. In sum up, the cancer-promoting function of LINC01296 was achieved by regulating the expression of miR-29c-3p, and LINC01296/miR-29c-3p axis mediates the mechanical regulation of EMT in OC cells, hoping to provide the novel biomarkers and possibilities for OC therapy.

Highlights

  • Ovarian cancer (OC), as one of gynecological malignant tumors, has the characteristics of high incidence, high recurrence rate and high mortality [1, 2]

  • MiR-29c-3p was predicted to be the target miRNA of LINC01296, which was lowly expressed in OC tissues and cell lines, causing unfavourable outcomes in OC Firstly, StarBase website was used to predict the target miRNA of LINC01296

  • From the analysis of data in GSE119055 database, we found that the expression of miR-29c-3p was obviously reduced in OC tissue than that in the normal ovarian tissue (Fig. 1a, P < 0.05)

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Summary

Introduction

Ovarian cancer (OC), as one of gynecological malignant tumors, has the characteristics of high incidence, high recurrence rate and high mortality [1, 2]. Due to the limitations of its diagnostic methods, it is difficult to diagnose the disease in the early stage, and 60% of patients are found in the advanced stage [3]. The five-year survival rate was 47% for all patients, while it was as low as 20% for patients with stage IV [2]. Lack of effective biomarkers for early OC diagnosis is the main reason for low survival rate [5], so it is urgent to figure out the pathological mechanism of OC and find effective molecular targets for diagnosis and treatment. We found that long intergenic non-coding RNA 01296 (LINC01296) can be used as a biomarker for diagnosis and prognosis of OC patients [6], but its mechanism remains unclear

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