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LSM12 facilitates the progression of colorectal cancer by activating the WNT/CTNNB1 signaling pathway

YAN ZHUANG1,#, CHUNLAN NING2,3,#, PENGFEI LIU4,#, YANPENG ZHAO5, YUE LI6, ZHENCHI MA6, LULING SHAN6, YINGZHE PIAO7, PENG ZHAO6,*, XUN JIN2,*

1 Department of Colorectal Oncology, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, 300060, China
2 Department of Biochemistry and Molecular Biology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, 300060, China
3 Tianjin Medical University, Tianjin, 300070, China
4 Department of Oncology, Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital, Tianjin, 300120, China
5 Tianjin Marvel Medical Laboratory, Tianjin Marvelbio Technology Co., Ltd., Tianjin, 300381, China
6 Department of Gastro Colorectal Oncology, Tianjin Cancer Hospital Airport Hospital, Tianjin, 300304, China
7 Department of Neuro-Oncology and Neurosurgery, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy Tianjin, Tianjin’s Clinical Research Center for Cancer, Tianjin, 300060, China

* Corresponding Authors: Xun Jin, email; Peng Zhao, email

Oncology Research 2022, 30(6), 289-300. https://doi.org/10.32604/or.2022.028225

Abstract

Aberrant activation of the WNT signaling pathway is a joint event in colorectal cancer (CRC), but the molecular mechanism is still unclear. Recently, RNA-splicing factor LSM12 (like-Sm protein 12) is highly expressed in CRC tissues. This study aimed to verify whether LSM12 is involved in regulating CRC progression via regulating the WNT signaling pathway. Here, we found that LSM12 is highly expressed in CRC patient-derived tissues and cells. LSM12 is involved in the proliferation, invasion, and apoptosis of CRC cells, similar to the function of WNT signaling in CRC. Furthermore, protein interaction simulation and biochemical experiments proved that LSM12 directly binds to CTNNB1 (also known as β-Catenin) and regulates its protein stability to affect the CTTNB1-LEF1-TCF1 transcriptional complex formation and the associated WNT downstream signaling pathway. LSM12 depletion in CRC cells decreased the in vivo tumor growth through repression of cancer cell growth and acceleration of cancer cell apoptosis. Taken together, we suggest that the high expression of LSM12 is a novel factor leading to aberrant WNT signaling activation, and that strategies targeting this molecular mechanism may contribute to developing a new therapeutic method for CRC.

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ZHUANG, Y., NING, C., LIU, P., ZHAO, Y., LI, Y. et al. (2022). LSM12 facilitates the progression of colorectal cancer by activating the WNT/CTNNB1 signaling pathway. Oncology Research, 30(6), 289–300.



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