Mechanism of RBM15 in the malignant proliferation of colorectal cancer cells through regulating the stability of LncRNA FGD5-AS1 via m6A modification

Lin Ma; Weihua Liu; Xin Wang; Dezheng Li; Chuankui Wei

doi:10.1016/j.yexcr.2024.114384

Mechanism of RBM15 in the malignant proliferation of colorectal cancer cells through regulating the stability of LncRNA FGD5-AS1 via m6A modification

Exp Cell Res. 2024 Dec 17:114384. doi: 10.1016/j.yexcr.2024.114384. Online ahead of print.

Authors

Lin Ma¹, Weihua Liu², Xin Wang¹, Dezheng Li¹, Chuankui Wei³

Affiliations

¹ Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Shandong First Medical University, Tai 'an, Shandong, 271000, China.
² Department of Gastro-Intestinal Tract, Qilu Hospital of Shandong University Dezhou Hospital, Dezhou, Shandong, 251100, China.
³ Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Shandong First Medical University, Tai 'an, Shandong, 271000, China. Electronic address: weichuankui123@163.com.

PMID: 39701357
DOI: 10.1016/j.yexcr.2024.114384

Abstract

Colorectal cancer (CRC) is the third most prevalent cancer all around the world. This study explored the mechanism of RBM15-mediated m6A modification in CRC cell malignant proliferation. The expression of RBM15, LncRNA FGD5-AS1, and HOXC10 was detected in CRC cells. m6A levels in cells and m6A enrichment on FGD5-AS1 RNA were analyzed. FGD5-AS1 RNA stability and localization in CRC cells were analyzed. The binding of LncRNA FGD5-AS1 to YBX1 and YBX1 to the HOXC10 promoter was analyzed. Combined experiments were conducted to validate the mechanism. Tumor xenografts in nude mice were used to verify the mechanism of RBM15 in vivo. RBM15 was highly expressed in CRC cells. RBM15 inhibition suppressed CRC cell proliferation and reduced PCNA expression. RBM15 increased m6A modification on FGD5-AS1 RNA, enhancing FGD5-AS1 stability and expression. FGD5-AS1 promoted HOXC10 expression by recruiting YBX1 to the HOXC10 promoter. YBX1 inhibition suppressed HOXC10 expression. Overexpression of FGD5-AS1 or HOXC10 partially reversed the alleviative effect of RBM15 inhibition on CRC cell proliferation. RBM15 downregulation attenuated in vivo CRC cell proliferation by inhibiting the FGD5-AS1/HOXC10 axis. In conclusion, RBM15 promotes the FGD5-AS1/HOXC10 axis via m6A modification to promote CRC cell proliferation.

Keywords: Colorectal cancer; FGD5-AS1; HOXC10; Proliferation; RBM15.