Feng Zhang,1,2,* Kai-Li Zhu,3,* Rui Chen,1,* Fei Su1,4 

1Department of Oncology, The First Hospital of Lanzhou University, Lanzhou, Gansu Province, 73000, People’s Republic of China; 2Department of Oncology, The First Hospital of Lanzhou University (The Branch Hospital of Donggang), Lanzhou, Gansu Province, 73000, People’s Republic of China; 3The First Clinical Medical College, Lanzhou University, Lanzhou, Gansu Province, 73000, People’s Republic of China; 4School of Basic Medical Sciences, Lanzhou University, Lanzhou, Gansu Province, 73000, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Fei Su, School of Basic Medical Sciences, Lanzhou University, No. 199, Donggang West Road, Chengguan District, Lanzhou City, Gansu Province, 730000, People’s Republic of China, Email Sufei19881216@163.com

Background: Aggressive biological behavior leads to unfavorable survival of colorectal cancer (CRC) patients. Dysregulation of TXNIP has been reported to be associated with the occurrence, proliferation and metastasis of malignancies such as liver cancer, lung cancer, kidney cancer, gastric cancer, and pancreatic cancer. MiR-424-5p has been reported as a negative regulator of TXNIP involved in lipopolysaccharide-induced acute kidney injury. And disordered Hippo pathway and YAP/TAZ-TEAD activity are related to tumor progression. The study was designed to clarify the function of miR-424-5p and thioredoxin interacting protein (TXNIP) in the progression of CRC.
Methods: The expression pattern of TXNIP and miR-424-5p was detected by immunohistochemistry, qRT-PCR and/or Western blotting. CCK-8 assays and transwell assays were applied to investigate the effect of TXNIP and miR-424-5p on cell proliferation, invasion and migration. Luciferase reporter assays were used to verify the transcriptional regulation among TXNIP, miR-424-5p and Hippo signaling pathway.
Results: TXNIP was poorly expressed whereas miR-424-5p was highly expressed in CRC tissues and cells. TXNIP overexpression suppressed proliferation, invasion and migration of CRC cells. It also suppressed the malignant behavior of the CRC cells promoted by miR-424-5p. Mechanically, TXNIP overexpression significantly inhibited YAP/TAZ transcriptional activity, and the highly expressed miR-424-5p in CRC targeted TXNIP mRNA.
Conclusion: The study clarify a novel miR-424-5p/TXNIP/Hippo signaling pathway that facilitated CRC cells proliferation, migration and invasion. The above findings suggested that miR-424-5p and TXNIP might serve as the potential therapeutic targets for CRC patients.

Keywords: CRC, thioredoxin interacting protein, miR-424-5p, YAP/TAZ signaling pathway