OCT4B1 Promoted EMT and Regulated the Self-Renewal of CSCs in CRC: Effects Associated with the Balance of miR-8064/PLK1

Jun-Min Zhou; Shui-Qing Hu; Hang Jiang; Yi-Lin Chen; Ji-Hong Feng; Zheng-Quan Chen; Kun-Ming Wen

doi:10.1016/j.omto.2019.08.004

OCT4B1 Promoted EMT and Regulated the Self-Renewal of CSCs in CRC: Effects Associated with the Balance of miR-8064/PLK1

Mol Ther Oncolytics. 2019 Aug 28:15:7-20. doi: 10.1016/j.omto.2019.08.004. eCollection 2019 Dec 20.

Authors

Jun-Min Zhou¹, Shui-Qing Hu¹, Hang Jiang¹, Yi-Lin Chen¹, Ji-Hong Feng², Zheng-Quan Chen¹, Kun-Ming Wen¹

Affiliations

¹ Department of Gastrointestinal Surgery, The Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563000, China.
² Department of Oncology, The Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563000, China.

Abstract

Cancer stem cells (CSCs) are the main cause of tumor generation, recurrence, metastasis, and therapy failure in various malignancies including colorectal cancer (CRC). Accumulating evidence suggests that tumor cells can acquire CSC characteristics through the epithelial-mesenchymal transition (EMT) process. However, the molecular mechanism of CSCs remains unclear. OCT4B1 is a transcript of OCT4, which is initially expressed in embryonic stem and carcinoma cells, and is involved in the regulation and maintenance of an undifferentiated state of stem cells. In this study, three-dimensional (3D) microspheres were confirmed as CRC stem cells. Compared with that of parental cells, their self-renewal ability was significantly increased, and OCT4B1 expression was increased and promoted the EMT process. The knockdown of OCT4B1 decreased the self-renewal of CSCs and reversed EMT. Moreover, OCT4B1 induced the expression of Polo-like kinase 1 (PLK1), which is a key regulator of EMT in tumor cells. Further examination showed that OCT4B1 regulated the miR-8064/PLK1 balance to exert its function. Taken together, our data suggest that OCT4B1 may be involved in regulating the self-renewal of colorectal CSCs through EMT, which is at least partially due to the miR-8064/PLK1 balance. This study indicates that OCT4B1 is a potential therapeutic target for CRC by targeting CSCs.

Keywords: EMT; OCT4B1; PLK1; cancer stem cell; colorectal cancer; miR-8064; self-renewal.