PMID- 31241217 OWN - NLM STAT- MEDLINE DCOM- 20200908 LR - 20200908 IS - 1097-4644 (Electronic) IS - 0730-2312 (Linking) VI - 120 IP - 11 DP - 2019 Nov TI - Circular RNA circPIP5K1A promotes non-small cell lung cancer proliferation and metastasis through miR-600/HIF-1alpha regulation. PG - 19019-19030 LID - 10.1002/jcb.29225 [doi] AB - Circular RNAs (circRNAs) have an important function in human diseases, especially in cancer. circRNA hsa_circ_0014130 (circPIP5K1A), a particularly abundant circRNA, participates in the tumorigenesis of non-small cell lung cancer (NSCLC), although the underlying regulatory mechanism remains unclear. Here, we investigated the circPIP5K1A role in NSCLC. Expression of circPIP5K1A in NSCLC cell lines was explored with quantitative real-time PCR. The effect of circPIP5K1A on NSCLC was evaluated with circPIP5K1A silencing, miR-600 mimic transfection, and hypoxia-inducible factor (HIF)-1alpha overexpression, followed by assessment of cell proliferation, metastasis, and tumorigenesis in nude mice. The subcellular localization of circPIP5K1A was evaluated via fluorescence in situ hybridization (FISH), and correlation between circPIP5K1A, miR-600, and HIF-1alpha was assessed by luciferase assay. The data demonstrated that circPIP5K1A expression was increased in NSCLC cells. FISH showed that circPIP5K1A localized to the cytoplasm. The circPIP5K1A knockdown suppressed NSCLC cell metastasis and proliferation by promoting expression of miR-600. Overexpression of miR-600 inhibited HIF-1alpha-mediated metastasis and proliferation of NSCLC cell by downregulating the endothelial mesenchymal transition-related proteins, Snail and vimentin, and upregulating E-cadherin. In vivo experiments illustrated that circPIP5K1A silence suppressed tumor growth and pulmonary metastasis. The circPIP5K1A may function as an miR-600 sponge to facilitate NSCLC proliferation and metastasis by promoting HIF-1alpha. A bifluorescein reporter experiment confirmed that miR-600 was the circPIP5K1A target, and miR-600 interacted with the 3' untranslated region of HIF-1alpha. These results show that circPIP5K1A acted as a tumor promoter through a novel circPIP5K1A/miR-600/HIF-1alpha axis, which provides candidate markers and therapeutic targets for NSCLC. CI - (c) 2019 Wiley Periodicals, Inc. FAU - Chi, Yongbing AU - Chi Y AD - Clinical Laboratory, Shanghai Pudong New Area Gongli Hospital, Shanghai, China. FAU - Luo, Qiancheng AU - Luo Q AD - Department of Emergency Medicine, Shanghai Pudong New Area Gongli Hospital, The Second Military Medical University, Shanghai, China. FAU - Song, Yuting AU - Song Y AD - Ningxia Medical University, Ningxia, China. AD - Sino-French Cooperative Central Lab, Shanghai Gongli Hospital, Secondary Military Medical University, Shanghai, China. FAU - Yang, Fangsong AU - Yang F AD - Anhui Gaolu Winery Staff Hospital, Bozhou, Shanghai, China. FAU - Wang, Ying AU - Wang Y AD - Department of Central Laboratory, Shanghai Gongli Hospital, The Second Military Medical University, Shanghai, China. FAU - Jin, Mingming AU - Jin M AUID- ORCID: 0000-0003-3574-2410 AD - Department of Central Laboratory, Shanghai Gongli Hospital, The Second Military Medical University, Shanghai, China. FAU - Zhang, Denghai AU - Zhang D AD - Department of Central Laboratory, Shanghai Gongli Hospital, The Second Military Medical University, Shanghai, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190626 PL - United States TA - J Cell Biochem JT - Journal of cellular biochemistry JID - 8205768 RN - 0 (Biomarkers, Tumor) RN - 0 (HIF1A protein, human) RN - 0 (Hypoxia-Inducible Factor 1, alpha Subunit) RN - 0 (MIRN600 microRNA, human) RN - 0 (MicroRNAs) RN - 0 (Neoplasm Proteins) RN - 0 (RNA, Circular) RN - 0 (RNA, Neoplasm) SB - IM MH - A549 Cells MH - Animals MH - Biomarkers, Tumor/genetics/metabolism MH - Carcinoma, Non-Small-Cell Lung/genetics/*metabolism/pathology MH - *Cell Proliferation MH - Humans MH - Hypoxia-Inducible Factor 1, alpha Subunit/genetics/*metabolism MH - Lung Neoplasms/genetics/*metabolism/pathology MH - Male MH - Mice MH - Mice, Inbred BALB C MH - MicroRNAs/genetics/*metabolism MH - Neoplasm Metastasis MH - Neoplasm Proteins/genetics/*metabolism MH - RNA, Circular/genetics/*metabolism MH - RNA, Neoplasm/genetics/*metabolism OTO - NOTNLM OT - circPIP5K1A OT - hypoxia-inducible factor-1alpha OT - miR-600 OT - non-small cell lung cancer OT - proliferation and metastasis EDAT- 2019/06/27 06:00 MHDA- 2020/09/09 06:00 CRDT- 2019/06/27 06:00 PHST- 2019/05/10 00:00 [received] PHST- 2019/06/06 00:00 [accepted] PHST- 2019/06/27 06:00 [pubmed] PHST- 2020/09/09 06:00 [medline] PHST- 2019/06/27 06:00 [entrez] AID - 10.1002/jcb.29225 [doi] PST - ppublish SO - J Cell Biochem. 2019 Nov;120(11):19019-19030. doi: 10.1002/jcb.29225. Epub 2019 Jun 26.