Circ_0043256 upregulates KLF2 expression by absorbing miR‐1206 to suppress the tumorigenesis of lung cancer

Abstract

Background Circular RNAs (circRNAs) have been reported to play roles in lung cancer development. The purpose of this work was to explore the function and mechanism of circ_0043256 in lung cancer tumorigenesis. Methods Quantitative real‐time polymerase chain reaction (qRT‐PCR) and western blot were used for the detection of the levels of genes and proteins. Cell growth, angiogenesis ability, migration, and invasion were analyzed by using 5‐ethynyl‐2′‐deoxyuridine (EdU) assay, flow cytometry, tube formation assay, transwell assay, and murine xenograft model, respectively. The target between miR‐1206 and circ_0043256 or Krüppel‐like factor 2 (KLF2) was verified by dual‐luciferase reporter assay. Results Circ_0043256 was a stable circRNA, which was found to be decreased in lung cancer tissues and cells. Functionally, forced expression of circ_0043256 suppressed lung cancer cell growth, angiopoiesis, migration, and invasion. Mechanistically, circ_0043256 directly bound to miR‐1206 and miR‐1206 targeted KLF2, circ_0043256 could regulate KLF2 expression via absorbing miR‐1206. Rescue assay showed that miR‐1206 overexpression reversed the anticancer effects of circ_0043256 on lung cancer cells. Moreover, inhibition of miR‐1206 could suppress the malignant phenotypes of lung cancer cells, which was attenuated by KLF2 knockdown. Pre‐clinically, lentivirus‐mediated circ_0043256 overexpression impeded lung cancer growth in nude mice. Conclusion Forced expression of circ_0043256 could impede the tumorigenesis of lung cancer via miR‐1206/KLF2 axis, indicating a potential therapeutic approach for lung cancer.

MicroRNA Expression Profiles in Human Samples and Cell Lines Revealed Nine miRNAs Associated with Cisplatin Resistance in High-Grade Serous Ovarian Cancer

“…Additionally, in the A549 and PC9 lung cancer cell lines, miR-1206 expression was greater than that in their noncancerous counterparts [31]. Inhibition of miR-1206 suppressed cell proliferation, blood vessel formation, migration, and invasion but increased apoptosis in A549 and PC9 lung cancer cell lines [31,38]. We observed a prominent reduction in the proliferation and invasion of OVCAR3CIS cells upon miR-1206 knockdown, and its reduced expression correlates well with ovarian cancer patient outcomes.…”

“…Gutierrez-Camino et al showed that miR-1206 is a potential biomarker for predicting methotrexate toxicity during chemotherapy treatment in pediatric acute lymphoblastic leukemia patients [30]. qRT-PCR of 36 pairs of tumor tissues and adjacent tissues collected from lung cancer patients revealed increased miR-1206 expression in the cancerous tissues [31]. Additionally, in the A549 and PC9 lung cancer cell lines, miR-1206 expression was greater than that in their noncancerous counterparts [31].…”

“…qRT-PCR of 36 pairs of tumor tissues and adjacent tissues collected from lung cancer patients revealed increased miR-1206 expression in the cancerous tissues [31]. Additionally, in the A549 and PC9 lung cancer cell lines, miR-1206 expression was greater than that in their noncancerous counterparts [31]. Inhibition of miR-1206 suppressed cell proliferation, blood vessel formation, migration, and invasion but increased apoptosis in A549 and PC9 lung cancer cell lines [31,38].…”

Non-coding RNAs in lung cancer: molecular mechanisms and clinical applications

“…Wang et al revealed that ZNRD1-AS1 upregulation increased tensin 1 levels by sponging miR-942, thereby suppressing LC angiogenesis (137). In addition, circ_0043256 upregulation remarkably repressed angiogenesis in LC cells by upregulating KLF2 via absorbing miR-1206 (138). In-depth investigations are needed to further clarify the ncRNA action in angiogenesis, which may bring significant advantage for the development of theoretical basis in LC treatment.…”