Overexpression of miRNA-221 promotes cell proliferation by targeting the apoptotic protease activating factor-1 and indicates a poor prognosis in ovarian cancer

Abstract

MicroRNAs are a class of small non-coding, endogenous RNAs involved in cancer development and progression. MicroRNA-221 (mir-221) has been reported to have both an oncogenic and tumor-suppressive role in human tumors, but the role of miR-221 in ovarian cancer is poorly understood. In the present study, the expression levels of miR-221 and the apoptosis protease activating factor 1 (APAF1) protein in 63 samples of ovarian cancer tissues and the cell lines, IOSE25, A2780, OVCAR3, SKOV3 and 3AO were detected by quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and western blot analysis, respectively. Cell proliferation was measured using Cell Counting kit-8 (CCK-8); cell migration and invasion were detected using a Transwell assay; cell apoptosis was evaluated by flow cytometry and Hoechst staining, and a luciferase assay was performed to verify a putative target site of miR-221 in the 3′-UTR of APAF1 mRNA. Expression of miR-221 was upregulated in ovarian cancer tissues. Patients with increased miR-221 expression levels had a reduced disease-free survival (P=0.0014) and overall survival (P=0.0058) compared with those with low miR-221 expression. Transfection of SKOV3 and A2780 cell lines with miR-221 inhibitor induced APAF1 protein expression, suppressed cell proliferation and migration and promoted tumor cell apoptosis. In conclusion, the APAF1 gene was confirmed as a direct target of miR-221 and overexpression of APAF1 suppressed ovarian cancer cell proliferation and induced cell apoptosis in vitro. These findings indicate that miR-221-APAF1 should be studied further as a potential new diagnostic or prognostic biomarker for ovarian cancer.

miR‑221 regulates proliferation and apoptosis of ovarian cancer cells by targeting BMF

“…Hong et al (22) conducted RT-qPCR detection and demonstrated that, compared with the healthy control populations, the expression of miR-221 in the peripheral blood of patients with ovarian cancer was abnormally increased, and its expression level was correlated with the disease stage of International Federation of Gynecology and Obstetrics and histopathological grading, with the higher the expression of miR-221, the lower the survival rate and prognosis of patients. Li et al (21) determined that the expression levels of miR-221 were significantly increased in ovarian cancer cells A2780, OVCAR3, SKOV3 and 3AO, compared with the immortalized ovarian epithelial IOSE25 cells; and compared with para-cancer tissues, the expression of miR-221 in the tumor tissues of patients with ovarian cancer was also increased abnormally, with the overall survival rate and progression-free survival rate of patients with higher expression of miR-221 being significantly lower than those in patients with low expression of miR-221. In the present study, the expression of miR-221 in tumor tissue of patients with ovarian cancer was significantly higher, compared with the para-cancer tissues, which may be carcinogenic factor in the occurrence of ovarian cancer, similar to the results obtained by Gadducci et al (25), Hong et al (22) and Li et al (21).…”

“…miRNA can regulate the translation of its target gene mRNA or degrade mRNA by regulating the post-transcriptional level, which is involved in the regulation of numerous biological functions, including cell proliferation, migration, invasion and apoptosis (13)(14)(15). miR-221 is a miRNA that is closely associated with tumorigenesis and serves a tumor-promoting role in a variety of tumor types, including breast (16), pancreatic (17), prostate (18,19) and non-small cell lung cancer (20), and miR-221 serves a role as a tumor suppressor gene (21). A number of studies have demonstrated that the expression of miR-221 in tumor tissue or peripheral blood of patients with ovarian cancer was significantly increased, indicating that miR-221 may serve a role of a cancer-promoting gene in the occurrence of ovarian cancer (21,22).…”

“…miR-221 is a miRNA that is closely associated with tumorigenesis and serves a tumor-promoting role in a variety of tumor types, including breast (16), pancreatic (17), prostate (18,19) and non-small cell lung cancer (20), and miR-221 serves a role as a tumor suppressor gene (21). A number of studies have demonstrated that the expression of miR-221 in tumor tissue or peripheral blood of patients with ovarian cancer was significantly increased, indicating that miR-221 may serve a role of a cancer-promoting gene in the occurrence of ovarian cancer (21,22). MicroRNA.org online (22) predicted that BMF was the possible target gene of miR-221.…”

Uncovering the potential of CD44v/SYNE1/miR34a axis in salivary fluids of oral cancer patients

“…Although this approach is extremely promising, the stability of RNA and miRNAs in the bodily fluids has been questioned time and again attributed to the numerous RNases compelling it to degrade quickly. Conversely, several reports showed stability and consistency of these cfRNAs and cfmiRNAs, thus supporting their potential to be used as a biomarker for various malignancies . In spite of there being several salivary and serum proteomic, metabolomics, genomic, and transcriptomic biomarkers that have been widely used and explored over the past decades, however, biomarker exclusively specific for OSCC is yet to be determined.…”

“…Conversely, several reports showed stability and consistency of these cfRNAs and cfmiRNAs, thus supporting their potential to be used as a biomarker for various malignancies. [15][16][17][18] In spite of there being several salivary and serum proteomic, metabolomics, genomic, and transcriptomic biomarkers 19 that have been widely used and explored over the past decades, however, biomarker exclusively specific for OSCC is yet to be determined. Hence, the unearthing of serum and salivary biomarkers is a dynamic and evolving field in the regime of oral squamous cell carcinoma.…”