Carbonic Anhydrase VIII (CAVIII) Gene Mediated Colorectal Cancer Growth and Angiogenesis through Mediated miRNA 16-5p

Mingli Hsieh; Pei-Ju Huang; Pei-Yu Chou; Shih-Wei Wang; Hsi-Chi Lu; Wei-Wen Su; Yuan-Chiang Chung; Min-Huan Wu

doi:10.3390/biomedicines10051030

Carbonic Anhydrase VIII (CAVIII) Gene Mediated Colorectal Cancer Growth and Angiogenesis through Mediated miRNA 16-5p

Biomedicines. 2022 Apr 29;10(5):1030. doi: 10.3390/biomedicines10051030.

Authors

Mingli Hsieh^{1

2}, Pei-Ju Huang³, Pei-Yu Chou^{2

4

5}, Shih-Wei Wang⁶, Hsi-Chi Lu^{2

7}, Wei-Wen Su⁸, Yuan-Chiang Chung^{9

10}, Min-Huan Wu^{2

4

5}

Affiliations

¹ Department of Life Science, Tunghai University, No. 1727, Sec. 4, Taiwan Boulevard, Taichung 407, Taiwan.
² Life Science Research Center, Tunghai University, No. 1727, Sec. 4, Taiwan Boulevard, Taichung 407, Taiwan.
³ Department of Family Medicine, Changhua Christian Hospital, Changhua 500, Taiwan.
⁴ Bachelor of Science in Senior Wellness and Sport Science, Tunghai University, No. 1727, Sec. 4, Taiwan Boulevard, Taichung 407, Taiwan.
⁵ Senior Life and Innovation Technology Center, Tunghai University, No. 1727, Sec. 4, Taiwan Boulevard, Taichung 407, Taiwan.
⁶ Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
⁷ Food Science Department and Graduate Institute, Tunghai University, Taichung 407, Taiwan.
⁸ Department of Gastroenterology and Hepatology, Changhua Christian Hospital, Changhua 500, Taiwan.
⁹ Department of Surgery, Cheng-Ching General Hospital, Taichung 407, Taiwan.
¹⁰ Department of Surgery, Kuang Tien General Hospital, Taichung 407, Taiwan.

Abstract

Carbonic anhydrase VIII (CAVIII) is a member of the CA family, while CA8 is the oncogene. Here we observed increased expression of CAVIII with high expression in colorectal cancer tissues. CAVIII is also expressed in more aggressive types of human colorectal cancer cells. Upregulated CAVIII expression in SW480 cell lines increased vascular endothelial growth factor (VEGF) and reduced miRNA16-5p. Conversely, knockdown of the CAVIII results in VEGF decline by up-regulated miRNA16-5p. Moreover, the collection of different grades of CAVIII expression CRC cells supernatant co-culture with endothelial progenitor cells (EPCs) promotes the ability of tube formation in soft agar and migration in the Transwell experiment, indicating that CAVIII might facilitate cancer-cell-released VEGF via the inhibition of miRNA16-5p signaling. Furthermore, in the xenograft tumor angiogenesis model, knockdown of CAVIII significantly reduced tumor growth and tumor-associated angiogenesis. Taken together, our results prove that the CAVIII/miR-16-5p signaling pathway might function as a metastasis suppressor in CRC. Targeting CAVIII/miR-16-5p may provide a strategy for blocking its metastasis.

Keywords: angiogenesis; carbonic anhydrase VIII; miR-16-5p; vascular endothelial growth factor.

Grants and funding

This study was supported by grants from Taiwan’s Ministry of Science and Technology (MOST 106-2632-B-029-001; 106-2320-B-029-002; 104-2632-B-029-001; 105-2632-B-029-001).