CircEZH2 miR-133b IGF2BP2 aggravates colorectal cancer progression via enhancing the stability of m6A modified CREB1 mRNA
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PROVIDER: PRJNA844242 | ENA |
REPOSITORIES: ENA
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Project description:Background: Aberrant expression of circular RNAs contributes to the initiation and progression of human malignancies, but the underlying mechanisms remain largely elusive. Methods: High throughput sequencing was performed to screen aberrantly expressed circRNAs or miRNAs in colorectal cancer and adjacent normal tissues. A series of gain and loss of function studies were conducted to evaluate the biological behaviors of CRC cells. RNA pulldown, mass spectrometry, RIP, qRT PCR, western blot, luciferase reporter assays and MeRIP seq analysis were further applied to dissect the detailed mechanisms. Results: Here, a novel circRNA named circEZH2 , was screened out by RNA seq in CRC tissues, whose expression is related to clinicpathological characteristics and prognosis in CRC patients. Biologically, circEZH2 facilitates the proliferation and migration of CRC cells in vitro and in vivo. Mechanistically, circEZH2 interacts with m6A reader IGF2BP2 and blocks its ubiquitination dependent degradation. Meanwhile, circEZH2 could serve as a competing endogenous RNA for miR 133b, resulting in the upregulation of IGF2BP2. Particularly, circEZH2 IGF2BP2 enhances the stability of CREB1 mRNA, thus aggravating CRC progression. Conclusions: Our findings not only reveal the pivotal roles of circEZH2 in modulating CRC progression, but also advocate for attenuating circEZH2 miR-133b IGF2BP2 CREB1 regulatory axis to combat CRC.
2022-06-04 | GSE205241 | GEO
Project description:Background: Aberrant expression of circular RNAs contributes to the initiation and progression of human malignancies, but the underlying mechanisms remain largely elusive. Methods: High throughput sequencing was performed to screen aberrantly expressed circRNAs or miRNAs in colorectal cancer and adjacent normal tissues. A series of gain and loss of function studies were conducted to evaluate the biological behaviors of CRC cells. RNA pulldown, mass spectrometry, RIP, qRT PCR, western blot, luciferase reporter assays and MeRIP seq analysis were further applied to dissect the detailed mechanisms. Results: Here, a novel circRNA named circEZH2 , was screened out by RNA seq in CRC tissues, whose expression is related to clinicpathological characteristics and prognosis in CRC patients. Biologically, circEZH2 facilitates the proliferation and migration of CRC cells in vitro and in vivo. Mechanistically, circEZH2 interacts with m6A reader IGF2BP2 and blocks its ubiquitination dependent degradation. Meanwhile, circEZH2 could serve as a competing endogenous RNA for miR 133b, resulting in the upregulation of IGF2BP2. Particularly, circEZH2 IGF2BP2 enhances the stability of CREB1 mRNA, thus aggravating CRC progression. Conclusions: Our findings not only reveal the pivotal roles of circEZH2 in modulating CRC progression, but also advocate for attenuating circEZH2 miR 133b IGF2BP2 CREB1 regulatory axis to combat CRC.
2022-06-04 | GSE205094 | GEO
Project description:Overactivated osteoclastogenesis leading to abnormal subchondral bone loss is the main feature of temporomandibular joint osteoarthritis (TMJOA). The role of N6-methyladenosine (m6A) in osteoclast differentiation in TMJOA remains unknown. Here, we found that an m6A reader IGF2BP2 was essential for mature osteoclasts induction. In TMJ tissues of TMJOA patients, the expression of IGF2BP2 was increased. Moreover, IGF2BP2 was augmented in subchondral bone of monosodium iodoacetate (MIA)–induced TMJOA mice. Igf2bp2 deficiency attenuated MIA-induced subchondral bone loss and suppressed osteoclast differentiation. Mechanistically, IGF2BP2 directly stabilized PPARγ and C-FOS mRNA to enhance the NFATC1 signaling, thereby inducing osteoclast maturation. Moreover, the stabilized PPARγ promoted the transcription of C-FOS, resulting in a further amplified signaling of NFATC1. In Igf2bp2-deficient cells, overexpression of PPARγ and C-FOS rescued the function of osteoclasts through restoring reduced levels of NFATC1. On the other hand, IGF2BP2/PPARγ/C-FOS axis facilitated the formation of osteoclasts by restoring the inhibited autophagy levels through the downregulation of ATG16L2. Using an IGF2BP2 inhibitor CWI1-2 hindered osteoclast formation and represented therapeutic effects for TMJOA. In summary, IGF2BP2 is essential in differentiation and maturation of osteoclasts and aggravates TMJOA via stabilizing PPARγ and C-FOS, which promoting NFATC1-mediated osteoclast signaling and ATG16L2-mediated autophagy.
2025-02-24 | GSE282855 | GEO
Project description:BackgroundAberrant expression of circular RNAs (circRNAs) contributes to the initiation and progression of human malignancies, but the underlying mechanisms remain largely elusive.MethodsHigh-throughput sequencing was performed to screen aberrantly expressed circRNAs or miRNAs in colorectal cancer (CRC) and adjacent normal tissues. A series of gain- and loss-of-function studies were conducted to evaluate the biological behaviors of CRC cells. RNA pulldown, mass spectrometry, RIP, qRT-PCR, Western blot, luciferase reporter assays and MeRIP-seq analysis were further applied to dissect the detailed mechanisms.ResultsHere, a novel circRNA named circEZH2 (hsa_circ_0006357) was screened out by RNA-seq in CRC tissues, whose expression is closely related to the clinicpathological characteristics and prognosis of CRC patients. Biologically, circEZH2 facilitates the proliferation and migration of CRC cells in vitro and in vivo. Mechanistically, circEZH2 interacts with m6A reader IGF2BP2 and blocks its ubiquitination-dependent degradation. Meanwhile, circEZH2 could serve as a sponge of miR-133b, resulting in the upregulation of IGF2BP2. Particularly, circEZH2/IGF2BP2 enhances the stability of CREB1 mRNA, thus aggravating CRC progression.ConclusionsOur findings not only reveal the pivotal roles of circEZH2 in modulating CRC progression, but also advocate for attenuating circEZH2/miR-133b/IGF2BP2/ CREB1 regulatory axis to combat CRC.
| S-EPMC9245290 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2022-06-04 | GSE205242 | GEO
Project description:HITS-CLIP is performed for the RNA-binding protein, IMP2/IGF2BP2, from E13.5 mouse brain.
2016-06-06 | E-MTAB-3636 | biostudies-arrayexpress
Project description:To investigate the binding targets of PTBP1 (PTB) and IGF2BP2 (IMP2) in glioma cells, we carried out an unbiased analysis of transcripts bound by PTBP1 and IGF2BP2 using enhanced crosslinking immunoprecipitation followed by high-throughput sequencing (eCLIP) in A172 glioma cells. We repeated the eCLIP method twice in each experiment, and found that the ratio of PTBP1 and IGF2BP2 binding mRNAs overlap was very high.
2022-01-02 | GSE192792 | GEO