Circ-ZKSCAN1 regulates FAM83A expression and inactivates MAPK signaling by targeting miR-330-5p to promote non-small cell lung cancer progression

Yuanyong Wang; Rongjian Xu; Dongyang Zhang; Tong Lu; Wanpeng Yu; Yang Wo; Ao Liu; Tianyi Sui; Jian Cui; Yi Qin; Yanting Dong; Xiaoliang Leng; Dezhi Kong; Wenxing Du; Zhangfeng Huang; Wenhao Su; Tianxiang Yuan; Xiao Sun; Jianxun Wang; Wenjie Jiao

doi:10.21037/tlcr.2019.11.04

Circ-ZKSCAN1 regulates FAM83A expression and inactivates MAPK signaling by targeting miR-330-5p to promote non-small cell lung cancer progression

Transl Lung Cancer Res. 2019 Dec;8(6):862-875. doi: 10.21037/tlcr.2019.11.04.

Authors

Yuanyong Wang^{1

2}, Rongjian Xu¹, Dongyang Zhang¹, Tong Lu^{1

2}, Wanpeng Yu^{2

3}, Yang Wo¹, Ao Liu¹, Tianyi Sui¹, Jian Cui¹, Yi Qin¹, Yanting Dong^{1

2}, Xiaoliang Leng¹, Dezhi Kong¹, Wenxing Du¹, Zhangfeng Huang¹, Wenhao Su¹, Tianxiang Yuan¹, Xiao Sun¹, Jianxun Wang^{2

3}, Wenjie Jiao¹

Affiliations

¹ Department of Thoracic Surgery, Affiliated Hospital of Qingdao University, Qingdao 266000, China.
² Center for Regenerative Medicine, Institute for Translational Medicine, College of Medicine, Qingdao University, Qingdao 266000, China.
³ School of Basic Medical Sciences, Qingdao University, Qingdao 266000, China.

Abstract

Background: Circular RNAs (circRNAs) belong to a new type of endogenous non-coding RNA and plays a key role in carcinogenesis. Circ-ZKSCAN1 (hsa_circ_0001727) has been proven to be a tumor-dependent circRNA. However, its role in non-small cell lung cancer (NSCLC) has been underreported.

Methods: The expression patterns of circ-ZKSCAN1 were determined using qRT-PCR in NSCLC samples and cell lines. Cell proliferation was examined utilizing the CCK-8 assay. Cell migration and invasion were evaluated using the Transwell assay. The combination of circ-ZKSCAN1 and miR-330-5p in NSCLC cells was analyzed by RNA pull-down and luciferase reporter assay. We used the bioinformatics software circbank, CircInteractome, TargetScan and Miranda to predict circRNA-miRNA and miRNA-mRNA interactions.

Results: Our results showed that circ-ZKSCAN1 was significantly up-regulated in NSCLC, closely related to malignant characteristics and poor prognosis, and clinically related to tumor size and clinical stage. Subsequent experiments showed that circ-ZKSCAN1 could inhibit the growth of NSCLC cells in vitro and in vivo. Importantly, circ-ZKSCAN1 can act as a sponge of carcinogenic miR-330-5p to increase the expression of FAM83A, resulting in the inhibition of MAPK signal transduction pathway, thus promoting the progress of NSCLC. Interestingly, the increase in FAM83A expression caused by circ-ZKSCAN1 overexpression could in turn promote the expression of circ-ZKSCAN1.

Conclusions: Circ-ZKSCAN1 is a key positive regulator of NSCLC, and clarifies the potential molecular mechanism of the new circ-ZKSCAN1/miR-330-5p/FAM83A feedback loop in promoting the progress of NSCLC.

Keywords: FAM83A; Non-small cell lung cancer (NSCLC); circ-ZKSCAN1; miR-330-5p; prognosis.