The lncRNA NEAT1 Inhibits miRNA-216b and Promotes Colorectal Cancer Progression by Indirectly Activating YY1

Yuping Zhu; Xuanying Wang; Linfeng Zheng; Dechuan Li; Zhuo Liu; Lisong Teng

doi:10.1155/2022/8130132

The lncRNA NEAT1 Inhibits miRNA-216b and Promotes Colorectal Cancer Progression by Indirectly Activating YY1

J Oncol. 2022 Oct 10:2022:8130132. doi: 10.1155/2022/8130132. eCollection 2022.

Authors

Yuping Zhu^{1

2}, Xuanying Wang³, Linfeng Zheng⁴, Dechuan Li², Zhuo Liu², Lisong Teng⁵

Affiliations

¹ Zhejiang University, Hangzhou 310058, China.
² Department of Colorectal Surgery, Cancer Hospital of the University of Chinese Academy of Sciences CHUCAS, Zhejiang Cancer Hospital, Hangzhou 310022, China.
³ Department of Integrated Chinese and Western Medicine, Cancer Hospital of the University of Chinese Academy of Sciences CHUCAS, Zhejiang Cancer Hospital, Hangzhou 310022, China.
⁴ Department of Pathology, Cancer Hospital, University of Chinese Academy of Sciences CHUCAS, Zhejiang Cancer Hospital, Hangzhou 310022, China.
⁵ Department of Surgery, First Affiliated Hospital of Zhejiang University, Hangzhou 310003, China.

Abstract

Background: Nuclear Paraspeckle Assembly Transcript 1 (NEAT1) is commonly considered an oncogene in various cancers. The long noncoding RNA NEAT1 has been reported to be overexpressed in colorectal cancer (CRC). However, the exact role of NEAT1 in CRC remains unknown. Our research aimed to explore the function of NEAT1 in the tumorigenesis and the development of CRC.

Methods: Real-time quantitative PCR (qRT-PCR) was used to detect the NEAT1, miR-216b, and YIN-YANG-1 (YY1) mRNA levels in CRC tissues and cells, then immunohistochemistry (IHC) was used to detect the expression of YY1 in CRC tissues. Luciferase reporter, qPCR, western blot, and DNA pulldown assays were conducted to study the relationships between NEAT1, miR-216b, and YY1. Flow cytometry analysis was performed for cell cycle and apoptosis analyses, and a colony formation assay was performed to test cell proliferation. Transwell assays were performed to detect cell invasion and migration.

Results: The NEAT1 expression was significantly upregulated in CRC tissues compared with its expression in normal tissues, and downregulation of NEAT1 suppressed the proliferation, migration, and invasion of CRC cells. Moreover, we found NEAT1 decreased the miR-216b level directly, and the suppression of miR-216b could inhibit the function of downstream YY1. However, overexpression of YY1 accelerated CRC cell proliferation, migration, and invasion.

Conclusion: Our results indicated that NEAT1 acted as an oncogene in CRC and promoted the progression of CRC by directly sponging miR-216 b expression to activate the expression of YY1. The NEAT1/miR-216b/YY1 axis may be a novel therapeutic target for CRC.