ZIC2 upregulates lncRNA SNHG12 expression to promote endometrial cancer cell proliferation and migration by activating the Notch signaling pathway

Cai,Pengyu; Li,Gaijuan; Wu,Mingxiu; Zhang,Bin; Bai,Hong

doi:10.3892/mmr.2021.12271

ZIC2 upregulates lncRNA SNHG12 expression to promote endometrial cancer cell proliferation and migration by activating the Notch signaling pathway

Authors:
- Pengyu Cai
- Gaijuan Li
- Mingxiu Wu
- Bin Zhang
- Hong Bai
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Affiliations: Department of Obstetrics and Gynecology, Dongguan People's Hospital, Dongguan, Guangdong 523000, P.R. China, Department of Obstetrics and Gynecology, Midwifery Profession, Shanxi Health Vocational College, Jinzhong, Shanxi 030600, P.R. China, The Second Ward of Gynecology, Dalian Obstetrics and Gynecology Hospital Affiliated to Dalian Medical University and Dalian Maternal and Child Health Care Hospital, Dalian, Liaoning 116033, P.R. China
Published online on: July 5, 2021 https://doi.org/10.3892/mmr.2021.12271
Article Number: 632
Copyright: © Cai et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

It was previously reported that long non‑coding RNA (lncRNA) small nucleolar RNA host gene 12 (SNHG12) promoted the proliferation, invasion and migration of endometrial cancer (EC) cells; however, the upstream underlying mechanism remains unclear. The present study aimed to determine the possible underlying mechanism of SNHG12 regulating EC. The Encyclopedia of RNA Interactomes database was used to analyze whether SNHG12 could bind to Zic family member 2 (ZIC2) and the expression levels of ZIC2 in patients with EC. ZIC2 expression levels in EC cell lines were analyzed using western blotting and reverse transcription‑quantitative PCR. RL95‑2 cells were subsequently transfected with short hairpin RNA targeting ZIC2, or ZIC2 or SNHG12 overexpression plasmids. Cell proliferation, migration and invasion were analyzed using Cell Counting Kit‑8, colony formation, wound healing and Transwell assays, respectively. The binding between ZIC2 and SHNG12 was verified using dual luciferase reporter and chromatin immunoprecipitation assays. The results of the present study revealed that the expression levels of ZIC2 were upregulated in the tissues of patients with EC and EC cell lines. ZIC2 knockdown inhibited RL95‑2 cell proliferation, migration and invasion. The protein expression levels of Ki67, proliferating cell nuclear antigen, MMP2 and MMP9 were also downregulated following the knockdown of ZIC2. ZIC2 was predicted to bind to SNHG12 and positively regulate SNHG12 expression. Further experiments demonstrated that the effects of the knockdown of ZIC2 on RL95‑2 cells were partially reversed by SNHG12 overexpression. In addition, ZIC2 knockdown inhibited Notch signaling activation, while SNHG12 overexpression reversed this effect. In conclusion, the findings of the present study indicated that ZIC2 may upregulate SNHG12 expression to promote EC cell proliferation and migration by activating the Notch signaling pathway.

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