Dataset Information

MiR-27a: A Novel Biomarker and Potential Therapeutic Target in Tumors.

ABSTRACT: MicroRNAs (miRNAs) are endogenous, time sequencing, conserved and small non-coding RNA molecules (19-25 bp long) that regulate gene expression at the post-transcriptional level by binding to the partial sequence homology of the 3'-untranslated region of target messenger (m)RNA. The miRNA-27 family consists of miR-27a and miR-27b, which are transcribed from different chromosomes and different in nucleotide at the 3' end. It has been reported that miR-27a was located on chromosome 19 and played a vital role in tumor development. Increasing evidences support a vital role for miR-27a in modulating polymorphisms, tumorigenesis, proliferation, apoptosis, invasion, migration and angiogenesis. Apart from it, miR-27a could affect drug sensitivity, treatment of cancer and patients prognosis. The miR-27a could be an oncogene or a tumor suppressor in several types of cancer, including colon cancer, pancreatic cancer, breast cancer, bladder cancer and hepatocellular carcinoma. In this review, we discuss the role of miR-27a in tumor biology and clinical significance in detail and offer novel insights into molecular targeting therapy for human cancers.

SUBMITTER: Li X

PROVIDER: S-EPMC6584939 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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MiR-27a: A Novel Biomarker and Potential Therapeutic Target in Tumors.

Li Xingwang X Xu Min M Ding Li L Tang Jinhai J

Journal of Cancer 20190602 12

MicroRNAs (miRNAs) are endogenous, time sequencing, conserved and small non-coding RNA molecules (19-25 bp long) that regulate gene expression at the post-transcriptional level by binding to the partial sequence homology of the 3'-untranslated region of target messenger (m)RNA. The miRNA-27 family consists of miR-27a and miR-27b, which are transcribed from different chromosomes and different in nucleotide at the 3' end. It has been reported that miR-27a was located on chromosome 19 and played a ...[more]

PMID: 31258791

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Project description:Bruton's tyrosine kinase (BTK) is a non-receptor intracellular kinase playing a key role in the proliferation and survival of normal and malignant B-lymphocytes. Its targeting by Ibrutinib, the first specific inhibitor, represented a turning point for the therapy of certain types of B-cell leukemias/lymphomas and several more BTK inhibitors are today in the clinic or advanced clinical trials. BTK expression was successively found to occur also outside of the hematopoietic compartment. In fact, we identified p65BTK, a novel 65 kDa isoform lacking an N-term stretch of 86 amino acids (compared to the 77 kDa protein expressed in B cells) as highly expressed in colon cancer patients. We demonstrated that p65BTK is a powerful oncogene acting downstream of the RAS/MAPK pathway and necessary for RAS-mediated transformation. Notably, the kinase domain is conserved and therefore inhibited by the available BTK-targeting drugs (Ibrutinib, Spebrutinib, etc.) which we used to demonstrate that p65BTK is an actionable target in drug-resistant colorectal carcinomas. We found p65BTK expressed also in >50% non-small cell lung cancers (NSCLC) and demonstrated that it is an actionable target in KRAS-mutated/EGFR-wild type drug-resistant NSCLC models (for which no targeted therapy is available). We also reported a significant correlation between p65BTK expression and low-grade tumors and overall survival of patients with grade III gliomas and showed that its targeting induced a significant decrease in the viability of in glioma stem cells. Finally, in ovarian cancer patients, p65BTK expression levels correlate with early relapse and shorter progression-free survival, both indicators of resistance to therapy. Remarkably, Ibrutinib is more effective than standard of care (SOC) therapeutics in in vitro and ex vivo settings. On the whole, our preclinical data indicate that, depending on the tumor type, BTK inhibitors used alone can induce cytotoxicity (gliomas), be more effective than SOC chemotherapy (ovarian cancer) or can kill drug-resistant tumor cells when used in combination with SOC chemotherapy (colon cancer and NSCLC) or targeted therapy (NSCLC and ovarian cancer), thus suggesting that p65BTK may be an actionable target in different solid tumors. In addition, our data also give the proof-of-concept for starting clinical trials using BTK inhibitors, alone or in combination, to improve the therapeutic options for solid tumors treatment.

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Dataset Information

MiR-27a: A Novel Biomarker and Potential Therapeutic Target in Tumors.

Publications

MiR-27a: A Novel Biomarker and Potential Therapeutic Target in Tumors.

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