PMID- 36966311
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230328
IS  - 1475-2867 (Print)
IS  - 1475-2867 (Electronic)
IS  - 1475-2867 (Linking)
VI  - 23
IP  - 1
DP  - 2023 Mar 25
TI  - A novel feedback regulated loop of circRRM2-IGF2BP1-MYC promotes breast cancer 
      metastasis.
PG  - 54
LID - 10.1186/s12935-023-02895-w [doi]
LID - 54
AB  - BACKGROUND: Metastasis is the leading cause of mortality in patients with breast 
      cancer (BC). Studies demonstrate that circular RNAs (circRNAs) were involved in 
      BC progression, while the molecular mechanisms remain largely unclear. METHODS: 
      The microArray circRNA profiles were used to explore the differential expression 
      circRNAs in BC and paracancerous normal tissues, and the quantitative reverse 
      transcription-polymerase chain reaction was used to validate their expression 
      level in clinical samples and cell lines. Nuclear/cytosolic fractionation and 
      fluorescence in situ hybridization (FISH) assays were performed to examine 
      circRRM2 (hsa_circ_0052582) subcellular location. The scratch wound healing and 
      transwell assays were conducted to evaluate the impact of circRRM2 on BC cell 
      migration and invasion. We predicted miRNAs that might bind with cricRRM2 and the 
      downstream target genes using bioinformatics analysis and explored their 
      expression levels and prognostic value in BC. FISH, RNA immunoprecipitation, 
      Co-immunoprecipitation, Western blot, and rescue experiments were implemented to 
      figure out circRRM2 function and underlying mechanisms in BC. RESULTS: The 
      present study revealed several aberrant circRNAs in BC tissues and observed that 
      circRRM2 was upregulated in tumor tissues of 40 patients with BC. High circRRM2 
      was significantly associated with advanced N stage in patients with BC. Gain- and 
      loss- of function experiments revealed that circRRM2 promoted the migration and 
      invasion of cells and functioned as an oncogene in BC. Mechanism studies showed 
      that circRRM2 competed with miR-31-5p/miR-27b-3p to upregulate the IGF2BP1 
      expression. Furthermore, IGF2BP1 upregulated the circRRM2 level via interacting 
      with MYC, which functioned as the transcriptional factor of circRRM2. Thus, the 
      positive feedback loop that was composed of circRRM2/IGF2BP1/MYC was identified. 
      CONCLUSION: This study confirms that upregulated circRRM2 functions an oncogenic 
      role in BC metastasis. The positive feedback loop of circRRM2/IGF2BP1/MYC 
      enforces the circRRM2 expression, which might offer a potential target for BC 
      treatment.
CI  - (c) 2023. The Author(s).
FAU - Hao, Ran
AU  - Hao R
AD  - Institutes of Health Research, Hebei Medical University, Shijiazhuang, Hebei, 
      China.
FAU - Zhang, Lei
AU  - Zhang L
AD  - Institutes of Health Research, Hebei Medical University, Shijiazhuang, Hebei, 
      China.
FAU - Si, Yangming
AU  - Si Y
AD  - School of Physical Science and Technology, Inner Mongolia University, Hohhot, 
      Inner Mongolia, China.
FAU - Zhang, Peng
AU  - Zhang P
AD  - Institutes of Health Research, Hebei Medical University, Shijiazhuang, Hebei, 
      China.
AD  - Department of Military Nursing, NCO School, Army Medical University, 
      Shijiazhuang, Hebei, China.
FAU - Wang, Yipeng
AU  - Wang Y
AD  - Institutes of Health Research, Hebei Medical University, Shijiazhuang, Hebei, 
      China.
FAU - Li, Bangchao
AU  - Li B
AD  - Department of Breast Center, The Fourth Hospital of Hebei Medical University, 
      Shijiazhuang, Hebei, China.
FAU - Hu, Jie
AU  - Hu J
AD  - Department of Science and Technology, Hebei Medical University, Shijiazhuang, 
      Hebei, China. Hujie@hebmu.edu.cn.
FAU - Qi, Yixin
AU  - Qi Y
AD  - Department of Breast Center, The Fourth Hospital of Hebei Medical University, 
      Shijiazhuang, Hebei, China. qiyixin@hebmu.edu.cn.
LA  - eng
GR  - H2020206483/Natural Science Foundation of Hebei Province/
GR  - H2021206289/Natural Science Foundation of Hebei Province/
GR  - 21377729D/S&T Program of Hebei/
GR  - 19277799D/S&T Program of Hebei/
PT  - Journal Article
DEP - 20230325
PL  - England
TA  - Cancer Cell Int
JT  - Cancer cell international
JID - 101139795
PMC - PMC10039515
OTO - NOTNLM
OT  - Breast cancer
OT  - Circular RNA
OT  - Feedback loop
OT  - MYC
OT  - Metastasis
COIS- The authors declare that there is no conflict of interests regarding the 
      publication of this paper.
EDAT- 2023/03/26 06:00
MHDA- 2023/03/26 06:01
PMCR- 2023/03/25
CRDT- 2023/03/25 23:25
PHST- 2022/08/03 00:00 [received]
PHST- 2023/03/08 00:00 [accepted]
PHST- 2023/03/25 23:25 [entrez]
PHST- 2023/03/26 06:00 [pubmed]
PHST- 2023/03/26 06:01 [medline]
PHST- 2023/03/25 00:00 [pmc-release]
AID - 10.1186/s12935-023-02895-w [pii]
AID - 2895 [pii]
AID - 10.1186/s12935-023-02895-w [doi]
PST - epublish
SO  - Cancer Cell Int. 2023 Mar 25;23(1):54. doi: 10.1186/s12935-023-02895-w.