Long Noncoding RNA HOXD-AS1 Promotes the Proliferation, Migration, and Invasion of Colorectal Cancer via the miR-526b-3p/CCND1 Axis

Colorectal Cancer
09/07/2020

Yan F, et al. J Surg Res 2020.

ABSTRACT

BACKGROUND: Colorectal cancer (CRC) is one of the most common malignancies in the world. It has been reported that the abnormal expression of long noncoding RNA HOXD-AS1 promotes the development of CRC, while the mechanism is still unclear. The aim of this study is to investigate the effects of HOXD-AS1 on proliferation, migration, and invasion in CRC and explore the underlying mechanism.

METHODS: Quantitative real-time polymerase chain reaction was used to detect the expression levels of HOXD-AS1, miR-526b-3p, and cyclin D1 (CCND1) in CRC tissues and cells. Dual-luciferase reporter assay was applied to examine the interaction between miR-526b-3p and HOXD-AS1 or CCND1. In addition, cell proliferation ability was assessed by Cell Counting Kit-8 assay. Cell migration and invasion abilities were determined using transwell assay. Furthermore, Western blot assay was conducted to measure the protein expression of CCND1.

RESULTS: HOXD-AS1 was highly expressed in CRC, and high expression of HOXD-AS1 was related to the poor prognosis of patients with CRC. MiR-526b-3p could be targeted by HOXD-AS1. Function experiment results revealed that miR-526b-3p inhibitor could reverse the suppressive effect of HOXD-AS1 knockdown on the proliferation, migration, and invasion of CRC cells. Moreover, CCND1 was a target of miR-526b-3p, and its overexpression could reverse the inhibitory effect of miR-526b-3p overexpression on the proliferation, migration, and invasion of CRC cells. In addition, CCND1 overexpression reversed the suppressive effect of HOXD-AS1 knockdown on the proliferation, migration, and invasion of CRC.

CONCLUSIONS: HOXD-AS1 upregulated the expression of CCND1 to promote the proliferation, migration, and invasion of CRC through targeting miR-526b-3p. This provided a new theoretical basis for clinical anticancer research of CRC.