Inhibition of miR-214-3p Aids in Preventing Epithelial Ovarian Cancer Malignancy by Increasing the Expression of LHX6

Abstract

In human epithelial ovarian cancer (EOC), various miRNAs can function as either oncogenes or tumor suppressor genes. We investigated miRNAs known to be involved in EOC progression and analyzed their expression in tissues and serum-derived exosomes from benign serous cystadenoma, borderline serous tumor, low-grade serous ovarian cancer, and high-grade serous ovarian cancer patients (HGSO). The HGSO group was divided based on the platinum-free interval, which is defined as the duration from the completion of platinum-based chemotherapy to recurrence. We also analyzed the mRNA levels of target genes that candidate miRNAs might regulate in patient tissues. miR-214-3p was highly expressed in tissues and exosomes derived from EOC with high malignancy and also found to regulate the expression of LIM homeobox domain 6 (LHX6) mRNA. Serum exosomal levels of miR-214-3p were significantly increased in platinum-resistant HGSO (25.2-fold, p < 0.001) compared to the exosomal expression of benign tumor patients. On transfection of miR-214-3p inhibitor in EOC cells, cell proliferation was inhibited while apoptotic cell death was increased. Collectively, we suggest that miR-214-3p in serum exosomes can be a potential biomarker for the diagnosis and prognosis of ovarian tumor, and its inhibition can be a supportive treatment for EOC.

Knockdown of SNHG14 Alleviates MPP+-Induced Injury in the Cell Model of Parkinson’s Disease by Targeting the miR-214-3p/KLF4 Axis

“…Among thousands of candidates predicted by the starBase software, miR-214-3p was fascinating because of its key role in multitudinous human diseases. For example, miR-214-3p regulated the tumorigenesis of ovarian cancer, endometrial cancer, and papillary thyroid carcinoma (Fang et al, 2019;Yang C. et al, 2019;Sui et al, 2020). MiR-214-3p was identified to repress cardiac fibrosis through the inhibition of the NOD-like receptor family CARD domain containing 5 (Yang K. et al, 2019).…”

Nucleic acids and proteins carried by exosomes of different origins as potential biomarkers for gynecologic cancers

“… 68 MiR-214-3p, which is an epigenetic regulator with an oncogenic role in EOC, 69 was highly expressed in serum exosomes from patients with highly malignant EOC and platinum-resistant high-grade serous ovarian cancer (HGSOC). 70 This study also demonstrated that the miR-214-3p and its target gene, LIM homeobox domain 6 (LHX6), in serum exosomes potentially acted as biomarkers for predicting EOC progression. 70 Moreover, Keseru et al.…”

“… 70 This study also demonstrated that the miR-214-3p and its target gene, LIM homeobox domain 6 (LHX6), in serum exosomes potentially acted as biomarkers for predicting EOC progression. 70 Moreover, Keseru et al. 71 detected the exosome-encapsulated mitochondrial DNA (mtDNA) copy number in the cell-free plasma of serous epithelial ovarian cancer patients, and indicated that the exosomal mtDNA copy number was increased in late-stage ( International Federation of Gynecology and Obstetrics [FIGO] stages III and IV) patients compared with the healthy individuals.…”

MiRNA-214 promotes the pyroptosis and inhibits the proliferation of cervical cancer cells via regulating the expression of NLRP3

“…In addition, miR-575-5p can also inhibit the growth of cervical cancer cells and enhance their sensitivity to chemotherapeutics by targeting QKI, a kind of RNA-binding protein. Furthermore, an increasing body of evidence suggested that miR-214 plays key roles in various diseases (22)(23)(24)(25)(26), which, nevertheless, has not yet covered the correlation between miR-214 and cell pyroptosis. In our study, miR-214 is downregulated obviously in cervical cancer, while the upregulation of miR-214 can decrease the pyroptosis of cervical cancer cell lines.…”