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Upregulated hsa_circ_0004458 Contributes to Progression of Papillary Thyroid Carcinoma by Inhibition of miR-885-5p and Activation of RAC1

Xiaoyan Jin, Zhengyi Wang, Wenyang Pang, Jian Zhou, Yong Liang, Jingjin Yang, Linjun Yang, Qiang Zhang

Department of Surgical Oncology, Zhejiang Taizhou Municipal Hospital, Taizhou, Zhejiang, China (mainland)

Med Sci Monit 2018; 24:5488-5500

DOI: 10.12659/MSM.911095

Available online:

Published: 2018-08-07

BACKGROUND: Circular RNAs (circRNAs), a class of noncoding RNAs, may act as biomarkers and therapeutic targets of various cancers. However, the effects of hsa_circ_0004458 in papillary thyroid carcinoma (PTC) are still very much unclear. We aimed to demonstrate the potential roles of hsa_circ_0004458 in the progression of PTC.
MATERIAL AND METHODS: In our study, qRT-PCR assay was performed to assess hsa_circ_0004458, miR-885-5p and RAC1 expressions. Dual-luciferase reporter assay was used to detect the regulatory effects of hsa_circ_0004458 on miR-885-5p, and miR-885-5p on RAC1. MTT and flow cytometry assays were used to measure the cell proliferation, cycle, and apoptosis abilities. Tumor formation assay in nude mice was performed to measure the tumor growth in vivo.
RESULTS: Our results indicated that hsa_circ_0004458 was upregulated in PTC tissues and cells, while silencing of hsa_circ_0004458 suppressed PTC cell proliferation and promoted PTC cell cycle arrest and apoptosis in vitro. Tumor formation assay in nude mice showed that knockdown of hsa_circ_0004458 by siRNAs inhibited the growth of PTC tumor in vivo. In addition, we found that miR-885-5p was a direct target of hsa_circ_0004458, and silencing of hsa_circ_0004458 inhibited PTC cell proliferation by miR-885-5p. We also demonstrated that RAC1 was a direct target of miR-885-5p and silencing of RAC1 suppressed PTC cell proliferation.
CONCLUSIONS: We found that hsa_circ_0004458 promoted the progression of PTC by inhibition of miR-885-5p and activation of RAC1, and hsa_circ_0004458 may serve as a potential therapeutic target and biomarker for PTC.

Keywords: Carcinoma, Papillary, rac1 GTP-Binding Protein, RNA, Untranslated