PMID- 35474604 OWN - NLM STAT- MEDLINE DCOM- 20220603 LR - 20230916 IS - 1759-7714 (Electronic) IS - 1759-7706 (Print) IS - 1759-7706 (Linking) VI - 13 IP - 11 DP - 2022 Jun TI - Activation of circ_0072088/miR-1261/PIK3CA pathway accelerates lung adenocarcinoma progression. PG - 1548-1557 LID - 10.1111/1759-7714.14369 [doi] AB - BACKGROUND: Circular RNAs (circRNAs) are involved in the tumorigenesis and progression of lung adenocarcinoma (LUAD). This study aimed to determine the role of circ_0072088 in LUAD. METHODS: The existence and expression of circ_0072088 in human LUAD tissues and cell lines were determined through Sanger sequencing, quantitative reverse transcription-polymerase chain reaction, and fluorescence in situ hybridization (FISH). Subsequently, the biological role of circ_0072088 was examined using loss-of-function assays in H1299 cells. Moreover, circ_0072088/miR-1261/PIK3CA pathway-mediated biological effects in H1299 were verified using bioinformatic prediction and experiments, including interaction analysis (FISH, luciferase reporter, and RNA-pulldown assays), and tumor biological function test (CCK8 and colony formation, wound healing, and transwell assays). Finally, miR-1261 and PIK3CA expression and LUAD patient survival were further analyzed using FISH, immunohistochemical staining, and the Kaplan-Meier plotter database, respectively. RESULTS: First, an increase in circ_0072088 was confirmed in human LUAD tissues. Thereafter, it was mainly localized in the cytoplasm and was found to enhance cell proliferation, migration, and invasion of H1299 cells. Mechanistically, circ_0072088 directly downregulated miR-1261 expression, whereas increased PIK3CA gene expression was associated with poor overall survival of LUAD patients. The activation of the circ_0072088/miR-1261/PIK3CA regulatory pathway may play a significant role in the tumorigenesis and progression of LUAD. CONCLUSIONS: Circ_0072088-dependent regulation of miR-1261/PIK3CA is important for cell proliferation, migration, and invasion during the tumorigenesis and progression of LUAD, warranting the need to consider the circ_0072088/miR-1261/PIK3CA regulatory pathway as a potential therapeutic target in patients with lung adenocarcinoma. CI - (c) 2022 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd. FAU - Cao, Feng AU - Cao F AUID- ORCID: 0000-0003-1604-1723 AD - Department of Radiation Oncology, the Fourth Hospital of HebeiMedical University, Shijiazhuang, China. FAU - Liu, Sihua AU - Liu S AD - Research Center, the Fourth Hospital of HebeiMedical University, Shijiazhuang, China. FAU - Li, Ziyi AU - Li Z AD - Research Center, the Fourth Hospital of HebeiMedical University, Shijiazhuang, China. FAU - Meng, Lingjiao AU - Meng L AD - Research Center, the Fourth Hospital of HebeiMedical University, Shijiazhuang, China. FAU - Sang, Meixiang AU - Sang M AD - Research Center, the Fourth Hospital of HebeiMedical University, Shijiazhuang, China. FAU - Shan, Baoen AU - Shan B AUID- ORCID: 0000-0003-4775-104X AD - Research Center, the Fourth Hospital of HebeiMedical University, Shijiazhuang, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220426 PL - Singapore TA - Thorac Cancer JT - Thoracic cancer JID - 101531441 RN - 0 (MicroRNAs) RN - 0 (RNA, Circular) RN - EC 2.7.1.137 (Class I Phosphatidylinositol 3-Kinases) RN - EC 2.7.1.137 (PIK3CA protein, human) SB - IM MH - *Adenocarcinoma of Lung/genetics/metabolism/pathology MH - Carcinogenesis MH - Cell Line, Tumor MH - Cell Proliferation/physiology MH - *Class I Phosphatidylinositol 3-Kinases/genetics MH - Disease Progression MH - Humans MH - In Situ Hybridization, Fluorescence MH - *Lung Neoplasms/genetics/metabolism/pathology MH - *MicroRNAs/genetics/metabolism MH - *RNA, Circular/genetics/metabolism MH - Signal Transduction PMC - PMC9161339 OTO - NOTNLM OT - bioinformatics OT - cell lines OT - circRNAs OT - lung adenocarcinoma OT - tumorigenesis COIS- The authors declare no conflict of interest, financial or otherwise. EDAT- 2022/04/28 06:00 MHDA- 2022/06/07 06:00 PMCR- 2022/06/01 CRDT- 2022/04/27 06:09 PHST- 2022/02/13 00:00 [revised] PHST- 2022/01/18 00:00 [received] PHST- 2022/02/14 00:00 [accepted] PHST- 2022/04/28 06:00 [pubmed] PHST- 2022/06/07 06:00 [medline] PHST- 2022/04/27 06:09 [entrez] PHST- 2022/06/01 00:00 [pmc-release] AID - TCA14369 [pii] AID - 10.1111/1759-7714.14369 [doi] PST - ppublish SO - Thorac Cancer. 2022 Jun;13(11):1548-1557. doi: 10.1111/1759-7714.14369. Epub 2022 Apr 26.