J Cancer 2021; 12(20):6145-6154. doi:10.7150/jca.60647 This issue

Research Paper

FOXD3-induced miR-133a blocks progression and metastasis of colorectal cancer through regulating UBA2

Yuanfang Cheng1, Yajuan Wang1, Yuanzun Cheng2, Quanzhong Yang1, Lejing Zhang1, Zhaoxi Li1, Jiancheng Cheng3✉

1. Sanquan College of Xinxiang Medical University, west of Changjiang Avenue, Pingyuan New Area, Xinxiang City, Henan Province, China.
2. College of Nursing, LuoYang Polytechic, Luoyang, 471000, Henan, China.
3. Department of Cardiovascular Surgery, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou 450000, China.

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Citation:
Cheng Y, Wang Y, Cheng Y, Yang Q, Zhang L, Li Z, Cheng J. FOXD3-induced miR-133a blocks progression and metastasis of colorectal cancer through regulating UBA2. J Cancer 2021; 12(20):6145-6154. doi:10.7150/jca.60647. Available from https://www.jcancer.org/v12p6145.htm

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Abstract

Graphic abstract

Background and Aim: Some studies have verified that miR-133a played an inhibitory role in several cancers. Whereas, the effect of miRNA-133a in colorectal cancer (CRC) has not been fully elucidated. Our study aims to confirm UBA2 as a direct target gene of miRNA-133a and explore the upstream modulatory molecules of miR-133a. In addition, their impacts on the biological characteristics of CRC cells were assessed.

Methods: QRT-PCR analyzed miR-133a expression levels in colorectal cells including HCT116, SW48 cells and human normal colorectal cell line NCM460. A serial biological experiment assessed miR-133a effects on cell proliferation, migration, invasion and apoptosis capacities in HCT116 and SW48 cells. MiRNA targeting gene prediction and a dual luciferase assay were employed to confirm miR-133a-targeted UBA2. Transcription factors (TFs) FOXD3 was identified as an upstream regulator of miR-133a via JASPAR. The influence of miR-133a and FOXD3 on UBA2 expression was analyzed by qRT-PCR or western blot.

Results: miR-133a was lowly expressed in CRC cells. High miRNA-133a expression suppressed the proliferation, migration, invasion and enhanced apoptosis capacities of CRC cells. MiR-133a targeted the UBA2 mRNA 3ʹUTR area and reduced UBA2 protein expression. We also unveiled that FOXD3 high-expression significantly raised miR-133a expression and diminished UBA2 expression. We also discovered that high miR-133a expression augmented the effects of elevated FOXD3 expression on CRC cell proliferation, migration and invasion, whereas, low miR-133a expression generated the opposite outcomes.

Conclusion: FOXD3 induced miRNA-133a directly targeting UBA2 could affect the progression and growth of CRC.

Keywords: MiR-133a, UBA2, Colorectal Cancer, FOXD3, GEO, ArrayExpress