Circ_RPL23A acts as a miR-1233 sponge to suppress the progression of clear cell renal cell carcinoma by promoting ACAT2.

Clear cell renal cell carcinoma (ccRCC) is a prevalent urological carcinoma with high metastatic risk. Circular RNAs (circRNAs) have been identified as effective diagnostic and therapeutic biomarkers for ccRCC. This research aims to disclose the effect and regulatory mechanism of circRNA ribosomal protein L23a (circ_RPL23A) in ccRCC. We performed quantitative real-time polymerase chain reaction (qRT-PCR) to examine circ_RPL23A, microRNA-1233 (miR-1233) and acetyl-coenzyme A acetyltransferase 2 (ACAT2). Cell cycle progression, apoptosis, cell viability, invasion and migration, which were respectively conducted by using flow cytometry, 3-(4, 5-dimethylthiazol-2-y1)-2, 5-diphenyl tetrazolium bromide (MTT), transwell assays. The levels of ACAT2 protein and cell cycle proteins, proliferation-associated protein, and epithelial-mesenchymal transition (EMT) associated proteins were measured by western blot. Target relationship was analyzed via dual-luciferase reporter assay and RNA pull down assay. The animal model was used to study how circ_RPL23A affects in vivo. Circ_RPL23A was lower expressed in ccRCC tissues and cells. The elevated circ_RPL23A suppressed cell cycle progression, proliferation, migration and invasion but promoted apoptosis in ccRCC cells. MiR-1233 was a target of circ_RPL23A and direct targeted to ACAT2. Besides, circ_RPL23A exerted its anti-tumor effect by sponging miR-1233, and then relieved the inhibition effect of miR-1233 on ACAT2. Overexpression of circ_RPL23A also curbed ccRCC tumor growth in vivo. Circ_RPL23A inhibited ccRCC progression by upregulating ACAT2 expression by competitively binding miR-1233, which might provide an in-depth cognition for ccRCC pathogenesis and circ_RPL23A might be a promising biomarker in ccRCC diagnosis and treatment.

CircTP53 promotes the proliferation of thyroid cancer via targeting miR-1233-3p/MDM2 axis.

BACKGROUND: Follicular cells give rise to thyroid cancer. Worldwide thyroid cancer incidence continues to rise in recent decades but the mortality rate remains at a stable level. The discovery of novel molecular mechanisms in the pathogenesis of thyroid cancer will promote new diagnostic or therapeutic strategies. Circular RNA (circRNA) is a type of noncoding RNA which is characterized by the covalently closed loop and non-protein coding capacity. The abnormal expression of circRNAs is an important part during the pathogenesis and development of thyroid cancer. CircTP53 is a novel circRNA, and we aimed to investigate its function in the pathogenesis of thyroid cancer and to further demonstrate the underlying molecular mechanism. METHODS: The levels of circTP53, miR-1233-3p, and other relative mRNA were analyzed by qRT-PCR. Protein levels were shown by Western blot. RNA-pulldown assay and luciferase assay were employed to examine the interaction between circTP53 and miR-1233-3p. Cell proliferation was analyzed by the MTT assay. RESULTS: CircTP53 was a circRNA highly expressed in thyroid cancer tissues. CircTP53 promoted cell proliferation and cell viability of TPC-1 cells. Knockdown of circTP53 inhibited the expression of Mouse double minute 2 (MDM2) and increased the protein level of p53. CircTP53 acted as a target of miR-1233-3p to increase MDM2 expression. p53 expression in thyroid cancer tissue exhibited a negative correlation with circTP53 expression. CONCLUSION: In thyroid cancer, overexpressed circTP53 decreased the protein level of p53 via targeting miR-1233-3p/MDM2 axis and promoted cancer cell proliferation.

CircEHMT1 inhibits metastatic potential of breast cancer cells by modulating miR-1233-3p/KLF4/MMP2 axis.

CircRNA is a kind of covalent head-to-tail looped RNA and plays an important role in tumor development. However, the identification of new potential targetable circRNAs to inhibit cancer development is still a huge challenge. In this study, we found that circEHMT1 inhibited migration and invasion of breast cancer cells. Mechanistically, we identified miR-1233-3p as a target of circEHMT1, and the circEHMT1/miR-1233-3p axis regulated matrix metalloprotease 2 (MMP2) by modulating the transcription factor Krϋppel-like factor 4 (KLF4). In summary, we showed that circEHMT1 has potential as a prognostic factor in breast cancer and played a tumor suppressor role via the circEHMT1/miR-1233-3p/KLF4/MMP2 axis.

Circular RNA hsa-circ-0007766 modulates the progression of Gastric Carcinoma via miR-1233-3p/GDF15 axis.

Circular RNAs (circRNAs), a new kind of non-coding RNAs, have gradually been proved to be critical regulators of gene expression; however, the underlying mechanisms still need to be elaborated. In the present study, we investigated the role of hsa-circ-0007766 in gastric carcinoma (GC). Quantitative real-time PCR was applied to detect the differential expression levels of circRNA, miRNAs, and mRNAs in human tissues and specific cell lines. GC cell lines were transiently transfected with siRNA. Then the proliferation, migration, and invasion assays were performed to evaluate the effect of hsa-circ-0007766 in GC cell lines. Fluorescence in situ hybridization, RNA pulldown assay was used to confirm the location of hsa-circ-0007766 and its relationship with miR-1233-3p. Luciferase reporter assay was then conducted to verify the interaction between miR-1233-3p and GDF15. Interestingly, we found that hsa-circ-0007766 was highly expressed in human GC tissues and GC cell lines. Knock-down of hsa-circ-0007766 inhibited cell proliferation, migration, invasion, and down-regulated the expression of GDF15. Moreover, hsa-circ-0007766 was identified as a sponge of miR-1233-3p, which could target gene GDF15 to regulate the progression of GC. Finally, hsa-circ-0007766 was evaluated to be a valuable diagnostic marker with a sensitivity of 53.33% and specificity of 83.33% by ROC analysis. This study unveils a mechanism by which hsa-circ-0007766 regulates GDF15 via hsa-circ-0007766/miR-1233-3p/GDF15 axis, which may provide new insight for GC therapeutic strategies.

Hsa_circ_0111738 Inhibits Tumor Progression and Angiogenesis in Multiple Myeloma by Sponging miR-1233-3p to Regulate HIF-1 Signaling Pathway.

BACKGROUND: Multiple myeloma (MM) presently remains largely incurable. The importance of circular RNAs (circRNAs) in various malignancies, including MM, has been demonstrated for decades. Our goal is to decipher the complex molecular mechanism of circ_0111738 in modulating MM progression. METHODS: Circ_0111738 and miR-1233-3p expressions in the collected MM cells and bone marrow aspirates were examined by qRT-PCR. CCK-8, transwell migration and invasion, and tube formation assays were performed to evaluate MM cell proliferation, migration and invasion, and angiogenesis, respectively. A tumor xenograft experiment was performed to validate the biofunction of circ_0111738's in vivo. The predicted interaction of circ_0111738 and miR-1233-3p's was determined by RNA immunoprecipitation (RIP) and luciferase reporter assays. Apoptosis-associated proteins and the HIF-1 pathway were investigated by western blotting. RESULTS: Circ_0111738 was poorly expressed in MM cells and patients. Overexpression of circ_0111738 reduced MM cell proliferation, migration, invasion, and angiogenesis while circ_0111738 led to opposite results. The anti-tumorigenic effect of circ_0111738 overexpression was also observed in vivo. RIP and luciferase experiments demonstrated that circ_0111738 interacted with miR-1233-3p in MM cells. The silencing of miR-1233-3p prevented the stimulation of malignant behaviors of MM cells induced by circ_0111738 silencing, including the expression of HIF-1α. CONCLUSION: Our data suggest that circ_0111738 functioned as a competing endogenous RNA (ceRNA) and suppressed the oncogenic function of miR-1233-3p in MM by inactivating the HIF-1 pathway. Therefore, up-regulation of circ_0111738 may be a promising therapy against MM.