LncRNA BBOX1-AS1 Aggravates the Development of Ovarian Cancer by Sequestering miR-361-3p to Augment PODXL Expression

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GYNECOLOGIC ONCOLOGY: ORIGINAL ARTICLE

LncRNA BBOX1-AS1 Aggravates the Development of Ovarian Cancer by Sequestering miR-361-3p to Augment PODXL Expression Huiping Yao 1 & Rui Chen 2 & Yongxiu Yang 1 & Juan Jiang 3 Received: 14 August 2020 / Accepted: 19 October 2020 # Society for Reproductive Investigation 2020

Abstract Ovarian cancer (OC) is a kind of common gynecological malignancy around the world. Mounting literatures have confirmed the implication of lncRNAs in the development of various cancers. Long non-coding RNA (LncRNA) BBOX1-AS1 has not been reported in most cancer types including OC. Presently, we aimed at exploring the function and regulatory mechanism of BBOX1AS1 in OC. As a result, we demonstrated the extremely high BBOX1-AS1 expression in OC tissues and cells. BBOX1-AS1 silence inhibited OC progression by suppressing cell proliferation and promoting cell apoptosis. Importantly, BBOX1-AS1 was verified to bind to miR-361-3p, which presented a low expression trend in OC cells. Subsequently, PODXL was testified as the downstream target of miR-361-3p. Of note, BBOX1-AS1 positively regulated PODXL through their competition in binding with miR-361-3p. Furthermore, miR-361-3p inhibition facilitated the growth of BBOX1-AS1-deficient OC cells, while such facilitating effect was then counteracted in response to PODXL depletion. All the results above explained that BBOX1-AS1 was overexpressed in OC and that BBOX1-AS1 caused carcinogenic influences on OC cell growth via miR-361-3p/PODXL pathway, highlighting BBOX1-AS1 as a novel potential target for OC treatment. Keywords BBOX1-AS1 . miR-361-3p . Ovarian cancer . PODXL

Introduction Ovarian cancer (OC) has become a primary cause of malignancy-related mortality among females around the world [1]. At present, the combined treatment of platinumbased chemotherapy and optical cytoreductive surgery is widely considered as the standard treatment for patients with early OC [2]. The survival rate of PC patients remains low, which is mainly attributed to the difficulty in early diagnosis and the obtained chemo-resistance resulting from frequent

Huiping Yao and Rui Chen are co-first authors. * Juan Jiang [email protected] 1

Department of Gynecology and Obstetrics, Gansu Key Laboratory of Gynecological Oncology, The First Hospital of Lanzhou University, Lanzhou, Gansu, China

2

Department of Gynecology, East Hospital Affiliated to Tongji University, Shanghai 200120, China

3

Department of Gynecology, People’s Hospital of Jingjiang, No. 28, Zhongzhou Road, Jingjiang 214500, Jiangsu, China

chemotherapy [3]. Hence, more effective treatments are in desperate need to be explored for OC. Non-coding RNAs transcribed from a large quantity of non-coding regions in the human genomes, including microRNAs (miRs) and lncRNAs, have no or limited potential to be translated into proteins [4]. In recent years, one point of view argues that lncRNAs are never transcriptional noise but own important cellular functions. Various lncRNAs have been verified to make a big difference in