Circ_0007031 Silencing Inhibits Cell Proliferation and Induces Cell Apoptosis via Downregulating MELK at a miR-485-3p-Dependent Way in Colorectal Cancer

Su, Shengtian; Lü, Wenjing; Liu, Jun; Li, Liping; Liu, Liang; Li, Xiaoju; Ye, Dan; Yu, Zhigao

doi:10.1007/s10528-021-10111-5

Cited by 12 publications

(5 citation statements)

References 47 publications

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“…There is growing evidence that circRNAs play an important role in the development of CRC as oncogenes or tumour suppressor genes. circRNAs are involved in different processes of tumour pathogenesis, including cell proliferation, migration, invasion, apoptosis, metastasis, epithelial mesenchymal transition (EMT) and cell cycle ( Yin et al, 2020 ; Zhang et al, 2021a ; Su et al, 2022 ). A summary analysis of the literature revealed that most circRNAs were associated with cancer cell proliferation ( n = 64), invasion ( n = 48), migration ( n = 49) and apoptosis ( n = 18), while a few cyclic RNAs were involved in cancer cell metastasis ( n = 9), cell cycle ( n = 5) and EMT ( n = 3) ( Figure 4 ).…”

Section: Resultsmentioning

confidence: 99%

Systematic analysis of circRNA biomarkers for diagnosis, prognosis and therapy in colorectal cancer

et al. 2022

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As the third most common cancer and the second leading cause of cancer death worldwide, colorectal cancer (CRC) poses a serious threat to people’s health. In recent years, circRNA has been widely reported as a new biomarker in CRC, but a comprehensive summary and analysis is lacking. This study aims to evaluate the diagnostic, therapeutic and prognostic significance of circRNAs in CRC by systematically analysing their expression patterns, biological functions and clinical significance in CRC. The literature on circRNA in CRC was searched in the PubMed database and included for analysis after screening according to strict inclusion and exclusion criteria. The UALCAN online tool was used to obtain host gene expression data. The miRTargetLink 2.0 was used to predict target genes for miRNAs action in CRC patients. Cytoscape was used to construct circRNA-miRNA-mRNA interaction networks. From the 236 included papers, we identified 217 circRNAs and their associated 108 host genes and 145 miRNAs. Among the 145 miRNAs, 27 miRNAs had no corresponding target genes. After prediction of target genes and differential analysis, a total of 25 target genes were obtained and a circRNA-miRNA-mRNA interaction network was constructed. Among the 217 circRNAs, 74 were associated with diagnosis, 160 with treatment and 51 with prognosis. And 154 of them function as oncogenes while 58 as tumour suppressor genes. In addition, these circRNAs include 32 exosomal circRNAs, which have unique advantages as biomarkers. In total, we summarize and analyze the expression patterns, biological functions and clinical significance of circRNAs in CRC. In addition, we constructed some new circRNA-miRNA-mRNA regulatory axes based on the miRNAs sponged by circRNAs.

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Section: Resultsmentioning

confidence: 99%

Systematic analysis of circRNA biomarkers for diagnosis, prognosis and therapy in colorectal cancer

et al. 2022

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“…Compared to miR-1246, fewer investigations have addressed the role of miR-485-3p in cancer, but, with few exceptions [ 65 , 66 , 67 ], it appears to function as a tumor-suppressor miRNA. Its expression in tumor tissue was found to be downregulated in prostate cancer [ 68 , 69 ], glioblastoma [ 70 ], breast and colorectal cancer [ 71 , 72 , 73 , 74 ], osteosarcoma [ 75 ] and renal carcinoma [ 76 ]. Interestingly, in some of those studies, the reduced expression of miR-485-3p was linked to upregulation of a long non-coding RNA (LncRNA) [ 75 ] or a circular RNA [ 72 , 74 , 76 ] able to sponge the miRNA, thus leading to enhanced expression of target genes promoting tumor cell proliferation, survival and invasiveness.…”

Section: Discussionmentioning

confidence: 99%

“…Its expression in tumor tissue was found to be downregulated in prostate cancer [ 68 , 69 ], glioblastoma [ 70 ], breast and colorectal cancer [ 71 , 72 , 73 , 74 ], osteosarcoma [ 75 ] and renal carcinoma [ 76 ]. Interestingly, in some of those studies, the reduced expression of miR-485-3p was linked to upregulation of a long non-coding RNA (LncRNA) [ 75 ] or a circular RNA [ 72 , 74 , 76 ] able to sponge the miRNA, thus leading to enhanced expression of target genes promoting tumor cell proliferation, survival and invasiveness. In the circulation, lower levels of miR-485-3p were detected in serum and serum exosome of glioblastoma patients as compared with healthy subjects [ 77 , 78 ].…”

Section: Discussionmentioning

confidence: 99%

“…In breast cancer cells, miR-485-3p was found to suppress migration, invasion and mitochondrial respiration by inhibiting the expression of the PGC-1A gene, which encodes a transcriptional coactivator that regulates genes involved in energy metabolism [ 71 ]. Other target genes whose negative modulation by miR-485-3p has been shown to impair tumor growth and metastasis include, among others, ZEB1 (Zinc Finger E-box Binding Homeobox 1) and BIRC5 (Baculoviral IAP Repeat Containing 5) in breast cancer cells [ 72 , 79 ], MELK (Maternal Embryonic Leucine Zipper Kinase) and JAK2 (Janus Kinase 2) in CRC cells [ 74 , 80 ], MET and AKT3 , in osteosarcoma cells [ 75 ].…”

Section: Discussionmentioning

confidence: 99%

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Circulating miR-1246 and miR-485-3p as Promising Biomarkers of Clinical Response and Outcome in Melanoma Patients Treated with Targeted Therapy

Levati

Bassi

Mastroeni

et al. 2022

Cancers

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Despite the significant improvements in advanced melanoma therapy, there is still a pressing need for biomarkers that can predict patient response and prognosis, and therefore support rational treatment decisions. Here, we investigated whether circulating miRNAs could be biomarkers of clinical outcomes in patients treated with targeted therapy. Using next-generation sequencing, we profiled plasma miRNAs at baseline and at progression in patients treated with BRAF inhibitors (BRAFi) or BRAFi + MEKi. Selected miRNAs associated with response to therapy were subjected to validation by real-time quantitative RT-PCR . Receiver Operating Characteristics (ROC), Kaplan–Meier and univariate and multivariate Cox regression analyses were performed on the validated miR-1246 and miR-485-3p baseline levels. The median baseline levels of miR-1246 and miR-485-3p were significantly higher and lower, respectively, in the group of patients not responding to therapy (NRs) as compared with the group of responding patients (Rs). In Rs, a trend toward an increase in miR-1246 and a decrease in miR-485-3p was observed at progression. Baseline miR-1246 level and the miR-1246/miR-485-3p ratio showed a good ability to discriminate between Rs and NRs. Poorer PFS and OS were observed in patients with unfavorable levels of at least one miRNA. In multivariate analysis, a low level of miR-485-3p and a high miR-1246/miR-485-3p ratio remained independent negative prognostic factors for PFS, while a high miR-1246/miR-485-3p ratio was associated with an increased risk of mortality, although statistical significance was not reached. Evaluation of miR-1246 and miR-485-3p baseline plasma levels might help clinicians to identify melanoma patients most likely to be unresponsive to targeted therapy or at higher risk for short-term PFS and mortality, thus improving their management.

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“…Mechanistically, it was identified that circ_0000338 directly interacts with and inactivates miR-217 and miR-485-3p [24] (Figure 1 and Table 1). It is known that miR-217 and miR-485-3p target mitogen-activated protein kinase 1 (MAPK1) and maternal embryonic leucine zipper kinase (MELK), respectively [25,26]. Since MAPK1 and MELK can promote 5-FU resistance [27,28], circ_0000338 may regulate drug sensitivity, partly via modulating the level of both MAPK1 and MELK.…”

Section: Exosomal Circrnasmentioning

confidence: 99%

Oncogenic Role of Exosomal Circular and Long Noncoding RNAs in Gastrointestinal Cancers

Yun

Choi

Son

et al. 2022

IJMS

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Circular RNAs (circRNAs) and long noncoding RNAs (lncRNAs) are differentially expressed in gastrointestinal cancers. These noncoding RNAs (ncRNAs) regulate a variety of cellular activities by physically interacting with microRNAs and proteins and altering their activity. It has also been suggested that exosomes encapsulate circRNAs and lncRNAs in cancer cells. Exosomes are then discharged into the extracellular environment, where they are taken up by other cells. As a result, exosomal ncRNA cargo is critical for cell–cell communication within the cancer microenvironment. Exosomal ncRNAs can regulate a range of events, such as angiogenesis, metastasis, immune evasion, drug resistance, and epithelial-to-mesenchymal transition. To set the groundwork for developing novel therapeutic strategies against gastrointestinal malignancies, a thorough understanding of circRNAs and lncRNAs is required. In this review, we discuss the function and intrinsic features of oncogenic circRNAs and lncRNAs that are enriched within exosomes.

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Circ_0007031 Silencing Inhibits Cell Proliferation and Induces Cell Apoptosis via Downregulating MELK at a miR-485-3p-Dependent Way in Colorectal Cancer

Cited by 12 publications

References 47 publications

Systematic analysis of circRNA biomarkers for diagnosis, prognosis and therapy in colorectal cancer

Systematic analysis of circRNA biomarkers for diagnosis, prognosis and therapy in colorectal cancer

Circulating miR-1246 and miR-485-3p as Promising Biomarkers of Clinical Response and Outcome in Melanoma Patients Treated with Targeted Therapy

Oncogenic Role of Exosomal Circular and Long Noncoding RNAs in Gastrointestinal Cancers

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