Circular RNA Paired-Related Homeobox 1 Promotes Gastric Carcinoma Cell Progression via Regulating MicroRNA-665/YWHAZ Axi
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ORIGINAL ARTICLE
Circular RNA Paired‑Related Homeobox 1 Promotes Gastric Carcinoma Cell Progression via Regulating MicroRNA‑665/YWHAZ Axis Wei Liu1 · Weigao Hu1 · Kezhu Hou1 · Song Zhu1 Received: 19 July 2020 / Accepted: 30 October 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Background Gastric carcinoma (GC) is a ubiquitous malignant tumor worldwide. Circular RNA paired-related homeobox 1 (circ-PRRX1), one kind of non-coding RNAs, has been reported to act as a promoter in tumor growth. This study aims to explore the effects of circ-PRRX1 on proliferation, apoptosis, and metastasis in GC and the underlying regulatory mechanisms. Methods The expression of circ-PRRX1, miR-665, and tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta (YWHAZ) mRNA was analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). Western blot was used to analyze YWHAZ protein expression. 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-Htetrazolium bromide (MTT), flow cytometry, and transwell assay were carried out to assess the viability, apoptosis, migration, and invasion in GC cells. The interaction between miR-665 and circ-PRRX1 or YWHAZ was predicted by StarBase v2.0 and identified by dual-luciferase reporter system. Xenograft mouse model was employed to determine the effects of circ-PRRX1 knockdown on GC growth in vivo. Results Compared with normal tissues and cells, circ-PRRX1 and YWHAZ levels were upregulated, and miR-665 was downregulated in GC tissues and cells. Functionally, circ-PRRX1 knockdown inhibited the viability, migration, and invasion and promoted apoptosis in GC cells, whereas anti-miR-665 abolished these effects. Mechanistically, circ-PRRX1 was confirmed as a sponge of miR-665 to regulate YWHAZ expression. Xenograft mouse model suggested that circ-PRRX1 knockdown reduced GC cells growth in vivo. Conclusion Circ-PRRX1 knockdown suppressed GC development by targeting miR-665 to inhibit YWHAZ expression, and the potential molecular mechanism may provide a theoretical basis for GC therapy. Keywords Gastric carcinoma · Circ-PRRX1 · MiR-665 · YWHAZ
Introduction According to the gastric carcinoma (GC) data submitted in 2014, the crude incidence of GC reached 278.07/100,000 in China, whereas the age-standardized incidence rate by world standard population (ASIRW) was Wei Liu and Weigao Hu have contributed equally to this work. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10620-020-06705-5) contains supplementary material, which is available to authorized users. * Song Zhu [email protected] 1
Department of General Surgery, Shidong Hospital, No. 999, Shiguang Road, Shanghai 200438, China
only 186.53/100,000. Moreover, the crude mortality of GC reached 167.89/100,000 in China, and differently, the ASIRW was 106.09/100,000 [1]. GC ranked third in cancer-related deaths in the world [2]. Several factors account for the incidence of GC, such as helicobacter pylori (HP) infection, heavy eating habits,
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