LINC01016 promotes the malignant phenotype of endometrial cancer cells by regulating the miR-302a-3p/miR-3130-3p/NFYA/SATB1 axis

Abstract

Long noncoding RNAs (lncRNAs) have been implicated in tumorigenesis and cancer progression and are tightly associated with the phenotypes of numerous cancers. However, the functional roles underlying these effects are unknown. The expression levels of LINC01016, miR-302a-3p, miR-3130-3p, NFYA, and SATB1 were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR) in 33 endometrial cancer tissues and 20 normal tissues. Bioinformatics analyses, luciferase reporter analyses, chromatin immunoprecipitation (ChIP) assays, and qRT-PCR assays were performed to verify potential binding sites. The qRT-PCR and western blot were used to identify the regulatory mechanisms of LINC01016 in cell biological behavior, which were also examined by cell counting kit -8 (CCK-8), 5-ethynyl-2′-deoxyuridine (EdU) assays, flow cytometry, wound healing assays, and transwell assays. LINC01016 was substantially upregulated in endometrial cancer tissues, and LINC01016 silencing abolished the malignant behavior of endometrial cancer cells. LINC01016 positively rescued the downstream gene nuclear factor YA (NFYA) by competitively “sponging” miR-302a-3p and miR-3130-3p. In turn, these two miRNAs could inhibit LINC01016 transcription, thus forming two reciprocal repression cycles, which influenced the biological behavior of endometrial cancer cells. MiR-302a-3p and miR-3130-3p could specifically bind with the 3′-UTR regions of NFYA, and NFYA could upregulate the expression of special AT-rich sequence-binding protein 1 (SATB1) as a transcriptional factor. This study was the first to show that the LINC01016–miR-302a-3p/miR-3130-3p/NFYA/SATB1 axis played a crucial role in the occurrence of endometrial cancer. These findings may provide relevant insights into the diagnosis and therapy of endometrial cancer.

Non-Coding RNAs in Endometrial Physiopathology

“…Another analysis found several circRNAs differentially expressed in EC cells when compared to normal endometrium [ 143 ]. In Table 3 , we present a list of significant lncRNAs deregulated in EC and the relative references [ 144 , 145 , 146 , 147 , 148 , 149 , 150 , 151 , 152 , 153 , 154 , 155 , 156 ].…”

<p>Silencing of Long Non-Coding RNA LINC01106 Suppresses the Proliferation, Migration and Invasion of Endometrial Cancer Cells Through Regulating the miR-449a/MET Axis</p>

“…Long non-coding RNAs (LncRNAs) are participated in modulating the tumorigenesis and progression of many human cancers, [6][7][8] including EC. [9][10][11] For instance, overexpression of LINC-ROR is reported to promote the growth of EC. 9 Up-regulation of LINC01016 accelerates the malignant biological behaviors of EC cells, such as increasing the proliferation and invasion abilities of EC cells.…”

BTG1 inhibits malignancy as a novel prognosis signature in endometrial carcinoma

“…According to the experimental method in our previous study, EdU cell proliferation assay kit (Ribobio, Guangzhou, China) was used to detect the effect of BTG1 on cell proliferation [31] . In a 96-well plate (Guangzhou Jet Bio-Filtration Co., Ltd. Guangzhou, China), 8000 cells were seeded per well.…”

“…According to the experimental method in our previous study [31] , we performed the Transwell invasion assay. Cells were imaged under an inverted uorescence microscope with an image acquisition system (Nikon, Japan).…”