miR‐153‐3p regulates progression of ovarian carcinoma in vitro and in vivo by targeting MCL1 gene

Abstract

The study of either miR‐153‐3p or MCL1 gene in ovarian carcinoma (OVC) has been reported; however, the interaction between miR‐153‐3p and MCL1 gene in OVC as well as the influence of their interaction on OVC progression has not been reported yet. Herein we intended to study the effects of miR‐153‐3p/MCL1 axis in OVC. Web‐based bioinformatics algorithms including DIANA TarBase 8.0, PicTar, and TargetScan Human 7.2 were used to predict the microRNAs (miRNAs) that could target MCL1 mRNA. Patient characteristics data collection and tissue sample immunohistochemical staining were used to determine the expression level of miR‐153‐3p and MCL1. We determined to unravel the effects of the pairing‐up of miR‐153‐3p and MCL1 mRNA in OVC cell lines (OVCAR3 cell line and A2780) and xenografts (immunodeficient(immunodeficient Rag−/− mice) using several methods including real‐time quantitative reverse transcription polymerase chain reaction, westernWestern blot, colony formation assay, wound healing assay, Transwell invasion assay, flow cytometry assay, and xenograft assay. These experiments were performed to study OVC cellular activities such as cell growth and death and so forth in vitro and in vivo. Plenty of miRNAs that can target MCL1 mRNA have been identified, and we have narrowed them down to miR‐153‐3p. MCL1 gene was found overexpressed in OVC tissues and OVC cell lines at RNA and protein levels, whereas miR‐153‐3p was found under‐expressed in OVC tissues and cells. miR‐153‐3p was found to target MCL1 mRNA and interfered OVC progression. The repression of MCL1 gene expression caused by either miR‐153‐3p or small interfering RNA technique led to significantly reduced OVC cell growth and invasion in vitro. Lastly, the engraftment of transfected human OVC cells into Rag−/− mice confirmed the in vitro results. MCL1 gene acts as a cancer facilitator in OVC. In this study, we revealed the role of miR‐153‐3p on OVC progression by targeting MCL1 gene. Our work could comprehend the current understanding of OVC progression and contribute to the underlying aggression mechanism of this cancer.

MicroRNA‑153‑3p suppresses retinoblastoma cell growth and invasion via targeting the IGF1R/Raf/MEK and IGF1R/PI3K/AKT signaling pathways

“…1B ). Previous studies have indicated that miR-153 functions as a tumor suppressor in several malignancies, such as non-small cell lung cancer (NSCLC) ( 21 ) and ovarian carcinoma (OC) ( 14 ). Therefore, miR-153 was selected for further analyses.…”

“…For example, miR-153 has been shown to target the inhibitor of growth protein 2 to inhibit acute lymphoblastic leukemia cell proliferation, migration and invasion ( 13 ). It has also been reported that miR-153 can inhibit the MCL1 gene, thus suppressing the progression of ovarian carcinoma in vitro and in vivo ( 14 ). In addition, miR-153 has been reported to inhibit the migration and the tube formation of endothelial cells by blocking the paracrine of angiopoietin 1 in breast cancer cells ( 15 ).…”

<p>lncRNA TMPO-AS1 Exerts Oncogenic Roles in HCC Through Regulating miR-320a/SERBP1 Axis</p>

“…MiRNAs modulate their target genes in a sequencespecific manner and their roles in cancers have been largely investigated. [27][28][29] Of note, SERBP1 was ascertained as a target of miR-320a. Importantly, TMPO-AS1 silencing and overexpression of miR-320a conspicuously lessened the mRNA level and protein expression of SERBP1 in HCC cell.…”

LncRNA OIP5-AS1 Affects the Malignant Biological Behavior of Ovarian Cancer via the miR-153-3p/KLF5 Axis

“…Mir-153-3p is a miRNA that plays a key role in disease progression. It has been reported that miR-153-3p plays an anticancer role in human cancers including melanoma [18] , gastric cancer [12] and ovarian cancer [3] . Through bioinformatics analysis, we found that KLF5 is the potential target gene of miR-153-3p.…”