Background:Triple-negative breast cancer (TNBC) accounts for 15–20% of all breast cancer in women globally. This subtype often has early and high recurrence rates, resulting in poor survival, partially due to lack of targeted therapies. To date, the detailed molecular mechanisms underlying TNBC progression are unclear. Given the crucial role of microRNAs (miRNAs) in cancer metastasis, we aimed to analyse the expression and function of a metastasis-associated miRNA named miR-211-5p in TNBC.Methods:MiRNA array analysis was performed to search for metastasis-associated miRNAs in TNBC. The miR-211-5p expression in tumour tissues, adjacent non-tumourous breast tissues of TNBC patients and cell lines were evaluated by real-time PCR. The protein expression levels were analysed by western blot, immunohistochemistry and in situ hybridisation. Luciferase reporter assays were employed to validate the target of miR-211-5p. The effect of miR-211-5p on TNBC progression was investigated in vitro and in vivo.Results:MiR-211-5p was significantly downregulated in TNBC, and its expression level was associated with overall survival in TNBC. The expression of miR-211-5p suppressed TNBC cell proliferation, invasion, migration and metastasis in vitro and in vivo. Furthermore, SETBP1 was identified as a target of miR-211-5p. Through gain-of-function and loss-of-function studies, SETBP1 was shown to significantly affect colony and cell number in vitro. Enforced expression of miR-211-5p inhibited the expression of SETBP1 significantly and the restoration of SETBP1 expression reversed the inhibitory effects of miR-211-5p on TNBC cell proliferation and metastasis.Conclusions:These findings collectively demonstrate a tumour suppressor role of miR-211-5p in TNBC progression by targeting SETBP1, suggesting that miR-211-5p could serve as a potential prognostic biomarker and therapeutic target for TNBC.
Collectively, SA3K protects against oxidative stress by targeting the ROS generation/degradation system and modulating the KEAP1-NRF2 signaling pathway.
The
desire for all-organic-composed nanoparticles (NPs) of considerable
biocompatibility to simultaneously diagnose and treat cancer is undeniably
interminable. Heretofore, metal-based agents dominate the landscape
of available magnetic resonance imaging (MRI) contrast agents and
photothermal therapeutic agents, but with associated metal-specific
downsides. Here, an all-organic metal-free nanoprobe, whose appreciable
biocompatibility is synergistically contributed by its tetra-organo-components,
is developed as a viable alternative to metal-based probes for MRI-guided
tumor-targeted photothermal therapy (PTT). This rationally entails
a glycol chitosan (GC)-linked polypyrrole (PP) nanoscaffold that provides
abundant primary and secondary amino groups for amidation with the
carboxyl groups in a nitroxide radical (TEMPO) and folic acid (FA),
to obtain GC-PP@TEMPO-FA NPs. Advantageously, the appreciably benign
GC-PP@TEMPO-FA features high nitroxide loading (r
1 = 1.58 mM–1 s–1)
and in vivo nitroxide-reduction resistance, prolonged
nitroxide-systemic circulation times, appreciable water dispersibility,
potential photodynamic therapeutic and electron paramagnetic resonance
imaging capabilities, considerable biocompatibility, and ultimately
achieves a 17 h commensurate MRI contrast enhancement. Moreover, its
GC component conveys a plethora of PP to tumor sites, where FA-mediated
tumor targeting enables substantial NP accumulation with consequential
near-complete tumor regression within 16 days in an MRI-guided PTT.
The present work therefore promotes the engineering of organic-based
metal-free biocompatible NPs in synergism, in furtherance of tumor-targeted
image-guided therapy.
Our observations suggest that serum miR-483-5p and miR-500a might serve as novel, noninvasive biomarkers for HCC. Serum miR-483-5p might complement AFP in detecting HCC.
The quest for an all‐organic nanosystem with negligible cytotoxicity and remarkable in vivo tumor theranostic capability is inescapably unending. Hitherto, the landscape of available photothermal agents is dominated by metal‐based nanoparticles (NPs) with attendant in vivo negatives. Here, an all‐organic‐composed theranostic nanosystem with outstanding biocompatibility for fluorescence image‐guided tumor photothermal therapy, and as a potential alternative to metal‐based photothermal agents is developed. This is rationally achieved by compartmentalizing indocyanine green (ICG) in glycol chitosan (GC)‐polypyrrole (PP) nanocarrier to form hybrid ICG@GC‐PP NPs (≈65 nm). The compartmentalization strategy, alongside the high photothermal conversion ability of PP jointly enhances the low photostability of free ICG. Advantageously, ICG@GC‐PP is endowed with an impeccable in vivo performance by the well‐known biocompatibility track records of its individual tri organo‐components (GC, PP, and ICG). As a proof of concept, ICG@GC‐PP NPs enables a sufficiently prolonged tumor diagnosis by fluorescence imaging up to 20 h post‐injection. Furthermore, owing to the complementary heating performances of PP and ICG, ICG@GC‐PP NPs‐treated mice by one‐time near‐infrared irradiation exhibit total tumor regression within 14 days post‐treatment. Therefore, leveraging the underlying benefits of this study will help to guide the development of new all‐organic biocompatible systems in synergism, for safer tumor theranostics.
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