LINC00665/miR-9-5p/ATF1 is a novel axis involved in the progression of colorectal cancer
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RESEARCH ARTICLE
LINC00665/miR‑9‑5p/ATF1 is a novel axis involved in the progression of colorectal cancer Xuhong Zhao1 · Wenhao Weng1 · Yin Long1 · Weijie Pan1 · Zhi Li1 · Fenyong Sun2 Received: 7 April 2020 / Accepted: 17 June 2020 © Japan Human Cell Society 2020
Abstract Long noncoding RNAs (lncRNAs) are abnormally expressed in many malignant tumors and involved in regulating the malignant phenotypes of cancer cells. However, the role of LINC00665 in colorectal cancer (CRC) and its regulatory mechanism remain unclear. In this study, real-time polymerase chain reaction (RT-PCR) was used to detect the expressions of LINC00665, miR-9-5p and activating transcription factor 1 (ATF1) mRNA in CRC tissues. The expression of ATF1 in CRC tissues was also detected by immunohistochemistry and Western blot. CCK-8 and colony formation assays were employed to detect cell proliferation. Cell cycle and apoptosis were detected by flow cytometry analysis. Scratch healing assay and Transwell test were exploited to detect cell migration and invasion. The targeting relationships between LINC00665 and miR-9-5p, and miR-9-5p and ATF1 were validated by dual luciferase reporter assay. We found that LINC00665 was significantly overexpressed in CRC tissues, and it was also negatively correlated with the expression of miR-9-5p and positively associated with the expression of ATF1. Besides, LINC00665 promoted the proliferation, migration and invasion of CRC cells, and inhibited cell apoptosis by sponging miR-9-5p. ATF1 was proved to be the downstream target of miR-9-5p and was indirectly regulated by LINC00665. Collectively, it is concluded that LINC00665 contributes to the progression of CRC by regulating miR-9-5p/ATF1 axis. Keywords CRC · LINC00665 · miR-9-5p · ATF1 Electronic supplementary material The online version of this article (https://doi.org/10.1007/s13577-020-00393-z) contains supplementary material, which is available to authorized users. * Zhi Li [email protected] * Fenyong Sun [email protected] Xuhong Zhao [email protected] Wenhao Weng [email protected] Yin Long [email protected] Weijie Pan [email protected] 1
Department of Clinical Laboratory, Yangpu Hospital, Tongji University School of Medicine, Shanghai 200090, People’s Republic of China
Department of Clinical Laboratory, Shanghai 10th People’s Hospital, Tongji University School of Medicine, No. 301 Middle Yanchang Road, Shanghai 200072, People’s Republic of China
2
Introduction Colorectal cancer (CRC) is one of the most common malignant tumors in the world and the third leading cause of cancer-related death [1, 2]. In recent years, the prognosis of CRC patients has been improved to some extent due to early diagnosis and comprehensive treatment [3–5]. However, the therapeutic effect for CRC is still unsatisfactory, as approximately 50% of CRC patients still suffer from the risk of distant metastasis or recurrence after surgery [6, 7]. Therefore, it is urgent to further explore the mechanism of CRC progression. Long non-coding RNAs (lnc
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