Repression of lncRNA PART1 attenuates ovarian cancer cell viability, migration and invasion through the miR-503-5p/FOXK1 axis

Abstract

Background Ovarian cancer (OC) is a female malignant tumor with a high fatality rate. Long non-coding RNAs (lncRNAs) are deeply involved in OC progression. The aim of this study is to explore the specific mechanism of lncRNA prostate androgen-regulated transcript 1 (PART1) in OC. Methods Quantitative real time PCR was utilized to determine the expression levels of PART1, microRNA (miR)-503-5p and forkhead-box k1 (FOXK1) in OC tissues and/or cells. The cell viability, migration, and invasion in OC were evaluated by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-h-tetrazolium bromide assay, wound healing assay and transwell invasion assay, respectively. Flow cytometry was used to analyze the cell apoptosis. The xenograft tumor was conducted in nude mice to verify the effect of PART1 knockdown on OC in vivo. The target relationships among PART1, miR-503-5p and FOXK1 were predicted by StarBase, and verified by luciferase reporter assay. The level of FOXK1 was assessed by western blot. Results Increased expression of PART1 and FOXK1 was observed in OC tissues or cells, whereas miR-503-5p was downregulated. PART1 silencing or miR-503-5p overexpression repressed the cell viability, migration and invasion, and protomed apoptosis. Meanwhile, miR-503-5p was a target of PART1, and FOXK1 was a direct target gene of miR-503-5p. Both downregulation of miR-503-5p and upregulation of FOXK1 partly relieved the suppressive effects of PART1 knockdown on the oncogenicity of OC in vitro. Conclusion Decreased PART1 represses the cell viability, migration and invasion of OC via regulating the miR-503-5p/FOXK1 axis, which provided an underlying target for treating OC.

Long non-coding RNA HOXA11-AS knockout inhibits proliferation and overcomes drug resistance in ovarian cancer

“…Cell pellets were washed twice with precooled PBS before adding 750 μL of binding buffer working solution to resuspend the cells. Cells were stained with Annexin V (Annexin V(FITC)) (5ul) and propidium iodide(PI) (5ul) in the dark for 15 min (minute) at room temperature [ 34 ]. Following the staining incubation, 400ul 1× Binding Buffer was added to each tube.…”

“…As described by Zhong, et al [ 34 ]. Radio immunoprecipitation (RIPA) buffer (Keygen Biotech) and phenylmethylsulfonyl fluoride were mixed at a 100:1 ratio.…”

FOXK1 upregulation is correlated with tumor progression and tumor associated macrophages infiltration in renal cell carcinoma

“…In recent years, mounting evidence has highlighted the regulatory roles of FOXK1 in various human diseases, particularly malignant tumors. For instance, studies have reported increased FOXK1 expression in ovarian cancer (OC) and its regulation by miR‐503‐5p, which affects the oncogenicity of OC 20 . In esophageal squamous cell carcinoma (ESCC), FOXK1 was found to be overexpressed and significantly enhanced cell proliferation, migration, and invasion 21 .…”

“…For instance, studies have reported increased FOXK1 expression in ovarian cancer (OC) and its regulation by miR-503-5p, which affects the oncogenicity of OC. 20 In esophageal squamous cell carcinoma (ESCC), FOXK1 was found to be overexpressed and significantly enhanced cell proliferation, migration, and invasion. 21 FOXK1 was also shown to be involved in the functions of lncRNA TRPM2-AS in cancer progression and paclitaxel resistance in prostate cancer.…”

Identification of LOC101927355 as a Novel Biomarker for Preeclampsia

“…In fact, the lncRNA LINC00551, which is downregulated in lung adenocarcinoma [ 35 ] and esophageal squamous cell carcinoma (ESCC) when silenced, promotes ESC cell proliferation, migration, and invasion in ESCC [ 36 ]. Prostate androgen-regulated transcript 1 (PART1) lncRNA can regulate the proliferation and invasion of prostate cancer cells [ 37 ] and breast cancer cells [ 38 , 39 , 40 ]. In the case of LINC00284, also known as non-coding RNA in the aldehyde dehydrogenase 1 A pathway (NRAD1), it is upregulated in ovarian [ 41 , 42 ] and breast cancer cells [ 43 ] and also involved in angiogenesis in ovarian cancer cells [ 41 ].…”