microRNAs (miRNAs) are emerging as important gene expression regulators linked to various biological processes at a posttranscriptional level. miRNAs have been known to play important roles in cell proliferation, cell differentiation, and apoptosis. Recently, accumulate studies indicate that up-regulation of miR-155 has been described in several types of human tumors. miR-155 has been considered to act as an oncogene or a tumor suppressor, depending on tumor system. Silencing oncomiRs or gene therapy approaches could be an effective therapeutic approach against tumor. Here we review the current knowledge on the functional role of miR-155 in the control of various cancers.
Drug resistance, including adriamycin (ADR)-based therapeutic resistance, is a crucial cause of chemotherapy failure in breast cancer treatment. Acquired chemoresistance has been identified to be closely associated with the overexpression of P-glycoprotein (P-gp/ABCB1). Long non-coding RNA (lncRNA) growth arrest-specific 5 (GAS5) can be involved in carcinogenesis; however, its roles in ABCB1-mediated ADR resistance are poorly understood. In this study, we identified a panel of differentially expressed lncRNAs, mRNAs, and mi-croRNAs (miRNAs) in MCF-7 and MCF-7/ADR cell lines through RNA sequencing (RNA-seq) technologies. GAS5 level was downregulated whereas ABCB1 level was upregulated in the resistant breast cancer tissues and cells. Overexpression of GAS5 significantly enhanced the ADR sensitivity and apoptosis, and it inhibited the efflux function and expression of ABCB1 in vitro, while knockdown of GAS5 had the opposite effects. Further mechanism-related investigations indicated that GAS5 acted as an endogenous "sponge" by competing for miR-221-3p binding to regulate its target dickkopf 2 (DKK2), and then it inhibited the activation of the Wnt/b-catenin pathway. Functionally, GAS5 enhanced the anti-tumor effect of ADR in vivo. Collectively, our findings reveal that GAS5 exerted regulatory function in ADR resistance possibly through the miR-221-3p/DKK2 axis, providing a novel approach to develop promising therapeutic strategy for overcoming chemoresistance in breast cancer patients.
Simultaneous [18F]-fluorodeoxyglucose positron emission tomography functional magnetic resonance imaging (FDG-PET/fMRI) provides the capacity to image 2 sources of energetic dynamics in the brain—glucose metabolism and the hemodynamic response. fMRI connectivity has been enormously useful for characterizing interactions between distributed brain networks in humans. Metabolic connectivity based on static FDG-PET has been proposed as a biomarker for neurological disease, but FDG-sPET cannot be used to estimate subject-level measures of “connectivity,” only across-subject “covariance.” Here, we applied high-temporal resolution constant infusion functional positron emission tomography (fPET) to measure subject-level metabolic connectivity simultaneously with fMRI connectivity. fPET metabolic connectivity was characterized by frontoparietal connectivity within and between hemispheres. fPET metabolic connectivity showed moderate similarity with fMRI primarily in superior cortex and frontoparietal regions. Significantly, fPET metabolic connectivity showed little similarity with FDG-sPET metabolic covariance, indicating that metabolic brain connectivity is a nonergodic process whereby individual brain connectivity cannot be inferred from group-level metabolic covariance. Our results highlight the complementary strengths of fPET and fMRI in measuring the intrinsic connectivity of the brain and open up the opportunity for novel fundamental studies of human brain connectivity as well as multimodality biomarkers of neurological diseases.
Simultaneous Magnetic Resonance Imaging (MRI) and Positron Emission Tomography (PET) scanning is a recent major development in biomedical imaging. The full integration of the PET detector ring and electronics within the MR system has been a technologically challenging design to develop but provides capacity for simultaneous imaging and the potential for new diagnostic and research capability. This article reviews state-of-the-art MR-PET hardware and software, and discusses future developments focusing on neuroimaging methodologies for MR-PET scanning. We particularly focus on the methodologies that lead to an improved synergy between MRI and PET, including optimal data acquisition, PET attenuation and motion correction, and joint image reconstruction and processing methods based on the underlying complementary and mutual information. We further review the current and potential future applications of simultaneous MR-PET in both systems neuroscience and clinical neuroimaging research. We demonstrate a simultaneous data acquisition protocol to highlight new applications of MR-PET neuroimaging research studies.
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