Circular RNA circHIPK2 inhibits colon cancer cells through miR-373-3p/RGMA axis.

Publisher: Elsevier Science Ireland Country of Publication: Ireland NLM ID: 7600053 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1872-7980 (Electronic) Linking ISSN: 03043835 NLM ISO Abbreviation: Cancer Lett Subsets: MEDLINE

Publication: Limerick : Elsevier Science Ireland
Original Publication: Amsterdam, Elsevier/North-Holland.

Cell Proliferation* ; Colonic Neoplasms*/genetics ; Colonic Neoplasms*/pathology ; Colonic Neoplasms*/metabolism ; Gene Expression Regulation, Neoplastic* ; MicroRNAs*/genetics ; MicroRNAs*/metabolism ; RNA, Circular*/genetics ; RNA, Circular*/metabolism; Animals ; Female ; Humans ; Male ; Mice ; Carrier Proteins ; Cell Line, Tumor ; Cell Movement ; Homeodomain Proteins/genetics ; Homeodomain Proteins/metabolism ; Intracellular Signaling Peptides and Proteins/genetics ; Intracellular Signaling Peptides and Proteins/metabolism ; Mice, Inbred BALB C ; Mice, Nude ; Nerve Tissue Proteins/genetics ; Nerve Tissue Proteins/metabolism ; Prognosis ; Protein Serine-Threonine Kinases/genetics ; Protein Serine-Threonine Kinases/metabolism ; Signal Transduction ; Transcription Factors/genetics ; Transcription Factors/metabolism

Circular RNAs (circRNAs) have been implicated in cancer development. However, their regulation, function, and underlying mechanisms of action remain unclear. We found that circHIPK2 was downregulated in colon cancer, and low expression levels of circHIPK2 were associated with high tumor grade and poor patient survival. The expression of circHIPK2 was observed to be regulated by the transcription factor HOXD10, which was downregulated in colon cancer. Consequently, low circHIPK2 expression promoted colon cancer cell proliferation, migration, and invasion in vitro and tumor growth and metastasis in vivo. Mechanistically, circHIPK2 sponges miR-373-3p to upregulate the expression of the tumor suppressor RGMA, leading to the activation of BMP/Smad signaling and, ultimately, the inhibition of colon cancer cells, indicating that circHIPK2 inhibits colon cancer cells through the miR-373-3p/RGMA/BMP pathway. These findings revealed a previously unknown regulation, function, and underlying mechanism of circHIPK2 in cancer cells. Hence, circHIPK2 may have a prognostic value and serve as a potential target for colon cancer treatment.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)

Keywords: Circular RNA; Colon cancer; Metastasis; MicroRNA; Tumor growth

0 (Carrier Proteins)
EC 2.7.1.- (HIPK2 protein, human)
0 (Homeodomain Proteins)
0 (Intracellular Signaling Peptides and Proteins)
0 (MicroRNAs)
0 (MIRN373 microRNA, human)
0 (Nerve Tissue Proteins)
EC 2.7.11.1 (Protein Serine-Threonine Kinases)
0 (RNA, Circular)
0 (Transcription Factors)
0 (RGMA protein, human)

Date Created: 20240518 Date Completed: 20240610 Latest Revision: 20240710

20240711

10.1016/j.canlet.2024.216957

38762192