Circulating microRNA-762 upregulation in colorectal cancer may be accompanied by Wnt-1/β-catenin signaling

Article type: Research Article

Authors: Lai, Peng-Sheng^a | Chang, Wei-Min^b | Chen, Ying-Yin^{c; d} | Lin, Yi-Feng^e | Liao, Hui-Fen^{e; f; 1; *} | Chen, Chung-Yu^{c; d; 1; *}

Affiliations: [a] Department of Surgery, National Taiwan University Hospital Yunlin Branch, Yunlin, Taiwan | [b] School of Oral Hygiene, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan | [c] Department of Internal Medicine, National Taiwan University Hospital Yunlin Branch, Yunlin, Taiwan | [d] College of Medicine, National Taiwan University, Taipei, Taiwan | [e] Department of Biochemical Science and Technology, National Chiayi University, Chiayi, Taiwan | [f] College of Chinese Medicine, China Medical University, Taichung, Taiwan

Correspondence: [*] Corresponding authors: Hui-Fen Liao, Department of Biochemical Science and Technology, National Chiayi University, 300 University Road, Chiayi 600, Taiwan. Tel.: +886 5 2717779; E-mail: [email protected]; Chung-Yu Chen, Department of Internal Medicine, National Taiwan University Hospital Yunlin Branch, Yunlin County, Taiwan, No. 579, Sec. 2, Yunlin Road, Douliu City, Yunlin County, 640, Taiwan. Tel.: +886 5 5323911, ext. 5675; E-mail: [email protected].

Note: [1] Hui-Fen Liao and Chung-Yu Chen contributed equally to this work.

Abstract: Colorectal cancer (CRC) has become the third most common cause of cancer-related deaths. CRC occurs because of abnormal growth of cells that can invade other tissues and cause distant metastases. Researchers have suggested that aberrant microRNA (miRNA) expression is involved in the initiation and progression of cancers. However, the key miRNAs that regulate the growth and metastasis of CRC remain unclear. The circulating miRNAs from BALB/c mice with CRC CT26 cell implantation were assayed by microarray. Then, Mus musculus (house mouse) mmu-miR-762 mimic and inhibitor were transfected to CT26 cells for analysis of cell viability, invasion, and epithelial-mesenchymal transition (EMT), cell cycle, and regulatory molecule expression. Human subjects were included for comparison the circulating Homo sapiens (human) has-miR-762 levels in CRC patients and control donors, as well as the patients with and without distant metastasis. The result for miRNA levels in mice with CRC cell implantation indicated that plasma mmu-miR-762 was upregulated. Transfection of mmu-miR-762 mimic to CT26 cells increased cell viability, invasion, and EMT, whereas transfection of mmu-miR-762 inhibitor decreased the above abilities. Cells treated with high-concentration mmu-miR-762 inhibitor induced cell cycle arrest at G0/G1 phase. However, mmu-miR-762 did not cause apoptosis of cells. Western blot analysis showed that mmu-miR-762 mimic transfection upregulated the expression of Wnt-1 and β-catenin, as well as increased the nuclear translocation of β-catenin. Further analysis was performed to demonstrate the correlation of miR-762 with CRC, and blood samples were collected from CRC patients and control donors. The results showed that serum has-miR-762 levels in CRC patients were higher than in control donors. Among the CRC patients (n= 20), six patients with distant metastasis showed higher serum has-miR-762 levels than patients without distant metastasis. Conclusions, the present study suggests that circulating miR-762 might be a potential biomarker for upregulation of CRC cell growth and invasion, and may be accompanied by the Wnt/β-catenin signaling.

Keywords: Colorectal cancer, distant metastasis, epithelial-mesenchymal transition (EMT), microRNA, Wnt/β-catenin

DOI: 10.3233/CBM-203002

Journal: Cancer Biomarkers, vol. 32, no. 2, pp. 111-122, 2021