Basic Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 21, 2019; 25(35): 5300-5309
Published online Sep 21, 2019. doi: 10.3748/wjg.v25.i35.5300
Circular RNA PIP5K1A promotes colon cancer development through inhibiting miR-1273a
Qu Zhang, Chi Zhang, Jian-Xin Ma, Hui Ren, Yu Sun, Jiao-Zhen Xu
Qu Zhang, Jiao-Zhen Xu, Department of Radiotherapy Center, Hubei Cancer Hospital, Wuhan 430079, Hubei Province, China
Chi Zhang, Department of Radiation Oncology, The First Affiliated Hospital of Nanjing Medical University/Jiangsu Province Hospital, Nanjing 210029, Jiangsu Province, China
Jian-Xin Ma, Department of Oncology, Lianyungang Municipal Oriental Hospital, Lianyungang 222042, Jiangsu Province, China
Hui Ren, Department of Chest Medicine, Hubei Cancer Hospital, Wuhan 430079, Hubei Province, China
Yu Sun, Department of Radiation Oncology, Wanbei Coal-Electricity Group General Hospital, Suzhou 234000, Anhui Province, China
Author contributions: Zhang Q performed the majority of experiments; Ma JX analyzed the data; Zhang C and Sun Y performed the molecular investigations; Xu JZ designed and coordinated the research; Ren H wrote the paper.
Supported by the National Natural Science Foundation of China, No. 81703028; and Hubei Cancer Hospital, No. 20162017B01.
Institutional review board statement: This study was reviewed and approved by the Hubei Cancer Hospital Ethics Committee.
Conflict-of-interest statement: The authors declare no conflict of interest.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Jiao-Zhen Xu, MSc, Attending Doctor, Department of Radiotherapy Center, Hubei Cancer Hospital, No. 116 Zhuodaoquan South Road, Hongshan District, Wuhan 430079, Hubei Province, China. fuposhuic51@163.com
Telephone: +86-27-190077000 Fax: +86-27-6003200
Received: May 16, 2019
Peer-review started: May 16, 2019
First decision: June 16, 2019
Revised: July 11, 2019
Accepted: July 19, 2019
Article in press: July 19, 2019
Published online: September 21, 2019
Processing time: 129 Days and 0.3 Hours
Abstract
BACKGROUND

Circular RNAs (circRNAs) are considered to be highly stable due to the closed structure, which are predominately correlated with the development and progression of a wide variety of cancers. Colon cancer is one of the most common malignancies worldwide. A recent study demonstrated the upregulated expression of circPIP5K1A in non-small cell lung cancer. However, few studies have investigated the relationship between circ_0014130 level and colon cancer. Therefore, elucidating the underlying mechanisms of circPIP5K1A’s role may help with the identification of novel diagnostic and therapeutic targets for colon cancer.

AIM

To investigate the status of circPIP5K1A in colon cancers and its effects on the modulation of cancer development.

METHODS

The expression level of circPIP5K1A in tissue and serum samples from colon cancer patients, as well as human colonic cancer cell lines was detected by real-time quantitative reverse transcription-polymerase chain reaction. Following the transfection of specifically synthesized small interfering RNA (siRNA) into colon cell lines, we used Hoechst staining assay to measure the ratio of cell death in the absence of circPIP5K1A. Moreover, we also used the Transwell assay to assess the migratory function of colon cells overexpressing circPIP5K1A. Additionally, we employed a series of bioinformatics prediction programs to predict the potential of circPIP5K1A-targeted miRNAs and mRNAs. The miR-1273a vector was constructed, and then transfected with or without circPIP5K1A vector into colon cancer cells. Afterwards, the expression of activator protein 1 (AP-1), interferon regulating factor 4 (IRF-4), caudal type homeobox 2 (CDX-2), and zinc finger of the cerebellum 1 (Zic-1) was detected by western blotting.

RESULTS

CircPIP5K1A was significantly upregulated in colon cancer tissue relative to their adjacent normal tissues. Knockdown of circPIP5K1A in colon cancer cells impaired cell viability and suppressed cell invasion and migration, while enforced expression of circPIP5K1A exhibited the opposite effects on cell migration. Bioinformatics prediction program predicted that the association of circPIP5K1A with miR-1273a, as well as AP-1, IRF-4, CDX-2, and Zic-1. Subsequent studies showed that overexpression of circPIP5K1A augmented the expression of AP-1 but attenuated the expression of IRF-4, CDX-2, and Zic-1. Reciprocally, overexpression of miR-1273a abrogated the oncogenic function of circPIP5K1A in colon cancers.

CONCLUSION

Overall, our data demonstrate the oncogenic role of circPIP5K1A-miR-1273a axis in regulation of colon cancer development, which provides a novel insights into colon cancer pathogenesis.

Keywords: Circular RNA PIP5K1A; miR-1273a; Cell death; Cell migration; Colon cancer

Core tip: We found that circular RNA PIP5K1A (circPIP5K1A) was selectively upregulated in colon cancer. Through sponging miR-1273a, circPIP5K1A promoted cell survival and enhanced the invasive and migratory functions of colon cancer cells, eventually exacerbating malignant transformation.