Achieving Optical Refractive Index of 10-Plus by Colloidal Self-Assembly.

This study demonstrates the developments of self-assembled optical metasurfaces to overcome inherent limitations in polarization density (P) and high refractive indices (n) within naturally occurring materials. The Maxwellian macroscopic description establishes a link between P and n, revealing a static limit in natural materials, restricting n to ≈4.0 at optical frequencies. Previously, it is accepted that self-assembly enables the creation of nanogaps between metallic nanoparticles (NPs), boosting capacitive enhancement of P and resultant exceptionally high n at optical frequencies. The work focuses on assembling gold (Au) NPs into a closely packed monolayer by rationally designing the polymeric ligand to balance attractive and repulsive forces, in that polymeric brush-mediated self-assembly of the close-packed Au NP monolayer is robustly achieved over a large-area. The resulting monolayer of Au nanospheres (NSs), nanooctahedras (NOs), and nanocubes (NCs) exhibits high macroscopic integrity and crystallinity, sufficiently enough for pushing n to record-high regimes. The systematic comparisons between each differently shaped Au NP monolayers elucidate the significance of capacitive coupling in achieving an unnaturally high n. The achieved n of 10.12 at optical frequencies stands as a benchmark, highlighting the potential of polyhedral Au NPs in advancing optical metasurfaces.

Somatic uniparental disomy mitigates the most damaging EFL1 allele combination in Shwachman-Diamond syndrome.

Shwachman-Diamond syndrome (SDS; OMIM #260400) is caused by variants in SBDS (Shwachman-Bodian-Diamond syndrome gene), which encodes a protein that plays an important role in ribosome assembly. Recent reports suggest that recessive variants in EFL1 are also responsible for SDS. However, the precise genetic mechanism that leads to EFL1-induced SDS remains incompletely understood. Here we present 3 unrelated Korean SDS patients who carry biallelic pathogenic variants in EFL1 with biased allele frequencies, resulting from a bone marrow-specific somatic uniparental disomy in chromosome 15. The recombination events generated cells that were homozygous for the relatively milder variant, allowing for the evasion of catastrophic physiologic consequences. However, the milder EFL1 variant was still solely able to impair 80S ribosome assembly and induce SDS features in cell line and animal models. The loss of EFL1 resulted in a pronounced inhibition of terminal oligopyrimidine element-containing ribosomal protein transcript 80S assembly. Therefore, we propose a more accurate pathogenesis mechanism of EFL1 dysfunction that eventually leads to aberrant translational control and ribosomopathy.

LINC00162 regulates cell proliferation and apoptosis by sponging PAQR4-targeting miR-485-5p.

Growing evidence indicates that long intergenic noncoding RNAs play an important role in cancer progression by affecting gene regulation at the transcriptional and posttranscriptional levels. Recent studies have shown that long intergenic noncoding RNA functions as a competitive endogenous RNA, which can interact with and mitigate the function of microRNA. In this study, we investigated the molecular mechanism by which LINC00162 regulates cell proliferation and apoptotic cell death. By analyzing RNA sequencing data, LINC00162 was identified to be a target of heterogeneous nuclear ribonucleoprotein K (hnRNPK). HnRNPK positively regulated LINC00162 expression through p38 mitogen-activated protein kinase. Lowering the level of either hnRNPK or LINC00162 decreased proliferation and colony formation while it increased apoptotic cell death. Small RNA sequencing followed by the antisense oligonucleotide pulldown, revealed that LINC00162 interacts directly with miR-485-5p which exhibited tumor-suppressing effects by suppressing cell proliferation and colony formation, and increasing apoptotic cell death. Through the bioinformatic approaches, progestin and adipoQ receptor 4 (PAQR4) was selected as a common target of LINC00162 and miR-485-5p. miR-485-5p decreased the expression of PAQR4 by directly binding to the 3'-untranslated region of PAQR4 messenger RNA. Knockdown of hnRNPK and LINC00162 increased the level of functional miR-485-5p, indicating that LINC00162 may compete for miR-485-5p, thereby derepressing PAQR4 expression. Overexpression of either hnRNPK or LINC00162, or inhibition of miR-485-5p, protected cells against etoposide-induced apoptotic death. Our findings demonstrate that a regulatory paradigm implicating hnRNPK, LINC00162, miR-485-5p, and PAQR4 plays an important role in cell proliferation and apoptosis, and is a promising target for cancer therapeutics.

Two circPPFIA1s negatively regulate liver metastasis of colon cancer via miR-155-5p/CDX1 and HuR/RAB36.

BACKGROUND: Circular RNAs (circRNAs) play a critical role in colorectal cancer (CRC) progression, including metastasis. However, the detailed molecular mechanism is not fully understood. METHODS: Differentially expressed circRNAs between primary KM12C and liver metastatic KM12L4 colon cancer cells were identified by microarray. The expression of circRNAs was measured by semi-quantitative (semi-qPCR) and real time-quantitative PCR (RT-qPCR). Metastatic potential including invasive and migratory abilities, and liver metastasis were examined by transwell assays and intrasplenic injection, respectively. CircPPFIA1-associated microRNA (miRNA) and RNA-binding protein (RBP) were screened by an antisense oligonucleotide (ASO) pulldown experiment. The effects of circPPFIA1 on target gene expression were evaluated by RT-qPCR and western blot analyses. RESULTS: By analyzing circRNA microarray data, we identified two anti-metastatic circRNAs generated from PPFIA1 with different length, which named circPPFIA1-L (long) and -S (short). They were significantly downregulated in liver metastatic KM12L4 cells compared to primary KM12C cells. The knockdown of circPPFIA1s in KM12C enhanced metastatic potential and increased liver metastasis. Conversely, overexpression of circPPFIA1s weakened metastatic potential and inhibited liver metastasis. circPPFIA1s were found to function as sponges of oncogenic miR-155-5p and Hu antigen R (HuR) by an ASO pulldown experiment. circPPFIA1s upregulated tumor-suppressing CDX1 expression and conversely downregulated oncogenic RAB36 by decoying miR-155-5p and by sequestering HuR, respectively. CONCLUSION: Our findings demonstrate that circPPFIA1s inhibit the liver metastasis of CRC via the miR-155-5p/CDX1 and HuR/RAB36 pathways.

Parallelization of Microfluidic Droplet Junctions for Ultraviscous Fluids.

The parallelization of multiple microfluidic droplet junctions has been successfully achieved so that the production throughput of the uniform microemulsions/particles has witnessed considerable progress. However, these advancements have been observed only in the case of a low viscous fluid (viscosity of 10-2 -10-3 Pa s). This study designs and fabricates a microfluidic device, enabling a uniform micro-emulsification of an ultraviscous fluid (viscosity of 3.5 Pa s) with a throughput of ≈330 000 droplets per hour. Multiple T-junctions of a dispersed oil phase, split from a single inlet, are connected into the single post-crossflow channel of a continuous water phase. In the proposed device, the continuous water phase undergoes a series circuit, wherein the resistances are continuously accumulated. The independent corrugations of the dispersed oil phase channel, under the theoretical guidance, compromise such increased resistances; the ratio of water to oil flow rates at each junction becomes consistent across T-junctions. Owing to the design being based on a fully 2D interconnection, single-step soft lithography is sufficient for developing the full device. This easy-to-craft architecture contrasts with the previous approach, wherein complicated 3D interconnections of the multiple junctions are involved, thereby facilitating the rapid uptake of high throughput droplet microfluidics for experts and newcomers alike.

MicroRNA-17-5p regulates EMT by targeting vimentin in colorectal cancer.

BACKGROUND: Epithelial-mesenchymal transition (EMT) is the most common cause of death in colorectal cancer (CRC). In this study, we investigated the functional roles of miRNA-17-5p in EMT of CRC cells. METHODS: In order to determine if miRNA-17-5p regulated EMT, the precursors and inhibitors of miR-17-5p were transduced into four CRC cells. To evaluate the regulatory mechanism, we performed argonaute 2 (Ago2) immunoprecipitation (IP) and luciferase assay. In addition, we used an intra-splenic injection mouse model of BALB/c nude mice to investigate the metastatic potential of miRNA-17-5p in vivo. RESULTS: The miRNA-17-5p expression was lower in primary CRC tissues with metastasis than in primary CRC tissues without metastasis in our RNA sequencing data of patient tissue. Real-time quantitative PCR revealed that miRNA-17-5p was inversely correlated with that of vimentin in five CRC cell lines. Over-expression of miRNA-17-5p decreased vimentin expression and inhibited cell migration and invasion in both LoVo and HT29 cells. However, inhibition of miRNA-17-5p showed the opposite effect. Ago2 IP and luciferase assay revealed that miRNA-17-5p directly bound to the 3'UTR of VIM mRNA. Furthermore, miRNA-17-5p inhibited the metastasis of CRC into liver in vivo. CONCLUSIONS: Our results demonstrated that miRNA-17-5p regulates vimentin expression, thereby regulating metastasis of CRC.

Correction: MicroRNA-17-5p regulates EMT by targeting vimentin in colorectal cancer.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Colloidal Photonic Assemblies for Colorful Radiative Cooling.

Radiative cooling has proven to be a powerful strategy for sustainable thermal management. Nanophotonic structures enabling broadband reflection lead to minimization of sunlight absorption, which has brought nighttime-limited radiative cooling into daytime applications. However, this broadband reflection strategy in turn restricts the accessible colorization of radiative coolers to white or neutral, consequently hindering their practical applications, particularly for aesthetic purposes. With a few exceptions, selective absorption at a specific visible wavelength has been the most prevalent paradigm for colorization of radiative coolers. However, this absorption-based colorization inevitably makes the radiative cooler prone to heating, thus decreasing the cooling efficiency. Here, we demonstrate an undiscovered usage of opals for advancing color-preserved daytime radiative coolers. Opals, which have served mainly as Bragg reflective color pigments thus far, can be considered an effective homogeneous medium in the mid-infrared region. Thus, opals can also be envisioned as reflectively colorful metamaterials capable of radiative cooling even under the direct summer sun. Together with the soft fluidity of colloidal suspensions, opals can serve as platforms for easy-to-craft, large-scale, and colorful radiative coolers with minimal solar absorption.

SRSF3-regulated miR-132/212 controls cell migration and invasion by targeting YAP1.

Although SRSF3 (Serine/arginine-rich splicing factor 3) plays a significant role in various biological processes, many of its functions still remain unclear. More particularly, little is known about SRSF3's involvement in the regulation of miRNA. In this report, we found that invasive and migratory abilities were inhibited in SRSF3-silenced U2OS and HeLa cells. We also found that a knockdown of SRSF3 results in a decreased expression level of REST (RE1-silencing transcription factor). The silencing of REST increased the expression of primary miR-132/212 as well as their mature forms. In particular, miR-132-3p and miR-212-3p possess an identical seed sequences and a common target gene. Overexpression of miR-132-3p and miR-212-3p suppressed the expression of YAP1 (Yes-associated protein 1) by directly binding to the 3՚UTR of its mRNA. CCND1 (Cyclin D1), which acts downstream of YAP1, was downregulated in both miR-132-3p and miR-212-3p-overexpressed cells, in correlation with diminished YAP1 levels. Taken together, our results reveal that SRSF3 controls the expression of the miR-132/212 cluster through regulating REST expression, and that the REST-elicited alteration of miRNA expression is implicated in enabling the migratory and invasive abilities of cancer cells.

Neurofibromatosis 2 (NF2) controls the invasiveness of glioblastoma through YAP-dependent expression of CYR61/CCN1 and miR-296-3p.

Glioblastoma multiforme (GBM) is the most common and aggressive type of primary brain tumor derived from non-neuronal glial cells. Neurofibromatosis 2 (NF2) protein, also termed as merlin, is a well-known tumor suppressor; however, the molecular mechanism underlying this effect has not yet been fully defined. To investigate the role of NF2 in the invasiveness of GBM, we used two GBM cell lines: NF2-expressing T98G cells and NF2-deficient A172 cells. Knockdown of NF2 increased the invasiveness of T98G cells, whereas NF2-overexpressing A172 cells showed decreased invasive activity. Moreover, re-expression of NF2 reversed the high invasiveness of NF2-silenced T98G cells, indicating that NF2 negatively regulates GBM invasiveness. We further found that the NF2-mediated regulation of invasiveness was dependent on YAP and TEAD2 expression levels. NF2 also controlled the expression of YAP targets, including cysteine-rich angiogenic inducer 61 (CYR61/CCN1), by regulating the nuclear localization of YAP. Silencing of CYR61/CCN1 blocked the increased invasiveness of T98G cells, suggesting that CYR61/CCN1 is required for NF2-mediated invasiveness. Through microRNA microarray analysis, we found that NF2 negatively regulates the expression of miR-296-3p. Overexpression of miR-296-3p suppressed the expression of STAT5A, induced the phosphorylation of STAT3 by downregulating SOCS2, and increased the invasiveness of T98G cells. Taken together, we demonstrate that NF2 negatively controls the invasiveness of GBM through YAP-dependent induction of CYR61/CCN1 and miR-296-3p.

LIN28A enhances the therapeutic potential of cultured neural stem cells in a Parkinson's disease model.

The original properties of tissue-specific stem cells, regardless of their tissue origins, are inevitably altered during in vitro culturing, lessening the clinical and research utility of stem cell cultures. Specifically, neural stem cells derived from the ventral midbrain lose their dopamine neurogenic potential, ventral midbrain-specific phenotypes, and repair capacity during in vitro cell expansion, all of which are critical concerns in using the cultured neural stem cells in therapeutic approaches for Parkinson's disease. In this study, we observed that the culture-dependent changes of neural stem cells derived from the ventral midbrain coincided with loss of RNA-binding protein LIN28A expression. When LIN28A expression was forced and sustained during neural stem cell expansion using an inducible expression-vector system, loss of dopamine neurogenic potential and midbrain phenotypes after long-term culturing was blocked. Furthermore, dopamine neurons that differentiated from neural stem cells exhibited remarkable survival and resistance against toxic insults. The observed effects were not due to a direct action of LIN28A on the differentiated dopamine neurons, but rather its action on precursor neural stem cells as exogene expression was switched off in the differentiating/differentiated cultures. Remarkable and reproducible behavioural recovery was shown in all Parkinson's disease rats grafted with neural stem cells expanded with LIN28A expression, along with extensive engraftment of dopamine neurons expressing mature neuronal and midbrain-specific markers. These findings suggest that LIN28A expression during stem cell expansion could be used to prepare therapeutically competent donor cells.

HuR recruits let-7/RISC to repress c-Myc expression.

RNA-binding proteins (RBPs) and microRNAs (miRNAs) are potent post-transcriptional regulators of gene expression. Here, we show that the RBP HuR reduced c-Myc expression by associating with the c-Myc 3' untranslated region (UTR) next to a miRNA let-7-binding site. Lowering HuR or let-7 levels relieved the translational repression of c-Myc. Unexpectedly, HuR and let-7 repressed c-Myc through an interdependent mechanism, as let-7 required HuR to reduce c-Myc expression and HuR required let-7 to inhibit c-Myc expression. Our findings suggest a regulatory paradigm wherein HuR inhibits c-Myc expression by recruiting let-7-loaded RISC (RNA miRNA-induced silencing complex) to the c-Myc 3'UTR.

An Optical Fiber Displacement Sensor Using RF Interrogation Technique.

We propose a novel non-contact optical fiber displacement sensor. It uses a radio frequency (RF) interrogation technique which is based on bidirectional modulation of a Mach-Zehnder electro-optical modulator (MZ-EOM). The displacement is measured from the free spectral range (FSR) which is determined by the dip frequencies of the modulated MZ-EOM transfer function. In experiments, the proposed sensor showed a sensitivity of 456 kHz/mm or 1.043 kHz/V in a measurement range of 7 mm. The displacement resolution of the proposed sensor depends on the linewidth and the power of the optical source. Resolution better than 0.05 µm would be achieved if an optical source which has a linewidth narrower than 1.5 nm and a received power larger than -36 dBm is used. Also, the multiplexing characteristic of the proposed sensor was experimentally validated.

Ischemic brain extract increases SDF-1 expression in astrocytes through the CXCR2/miR-223/miR-27b pathway.

Ischemic cerebral stroke is one of the leading global causes of mortality and morbidity. Ischemic preconditioning (IPC) refers to a sublethal ischemia and resulting in tolerance to subsequent severe ischemic injury. Although several pathways are reportedly involved in IPC-mediated neuroprotection, the functional role of astrocytes is not fully understood. Stromal cell-derived factor-1 (SDF-1), a CXC chemokine produced mainly in astrocytes, is a ligand for chemokine receptor CXCR4. SDF-1 is reported to play a critical role in neuroprotection after stroke by mediating the migration of neuronal progenitor cells. We hypothesized that stimuli derived from ischemic brain were involved in the protective effects of IPC. To investigate this hypothesis, the mechanism in which ischemic brain extract (IBE) induced SDF-1 expression was investigated in C6 astrocytoma cells. IBE treatment of C6 cells increased SDF-1 expression compared to that in untreated or normal brain extract (NBE)-treated cells by downregulating SDF-1 targeting miRNA, miR-27b. MiR-223 was inversely upregulated in IBE-treated cells; overexpression of miR-223 decreased the expression of miR-27b by suppressing IKKα expression. Analysis of cytokine array data revealed an IBE associated enhanced expression of CINC-1 (CXCL1) and LIX1 (CXCL5). Knockdown or inhibition of their receptor, CXCR2, abolished IBE-mediated increased expression of SDF-1. These results were confirmed in primary cultured astrocytes. Taken together, the data demonstrate that IBE-elicited signals increase SDF-1 expression through the CXCR2/miR-223/miR-27b pathway in C6 astrocytoma cells and primary astrocytes, supporting the view that increased expression of SDF-1 by ischemic insults is a possible mechanism underlying therapeutic application of IPC.

CD10 expression is enhanced by Twist1 and associated with poor prognosis in esophageal squamous cell carcinoma with facilitating tumorigenicity in vitro and in vivo.

CD10 expression was identified as a contributor to cancer progression in several cancers; however, the exact biological significance and mechanism of CD10 expression remains unclear. In addition, CD10 expression in esophageal squamous cell carcinoma (ESCC) has not been studied. We investigated the relationship between CD10 and Twist1. Furthermore, we examined the effect of CD10 on tumorigenicity using in vivo and in vitro systems as well as establishing the clinical significance of CD10 expression in ESCC using large clinical samples. CD10 expression was upregulated by Twist1 and there was a strong correlation between mRNA and protein expression. Twist1 can specifically upregulate CD10 at the transcriptional level via an interaction with the promoter region of CD10 and the proximal E-box CAGGTG in the CD10 promoter was identified as a binding site for Twist1. CD10 is frequently expressed in ESCC cell lines and silencing CD10 suppresses migration/invasion and anchorage-independent tumor growth of ESCC cells. Knockdown of CD10 inhibits the growth of ESCC xenograft in nude mice, suggesting that CD10 plays a role in enhancing the tumorigenesis of ESCC. From among 153 ESCC samples, 46 (30.0%) showed varying degrees of CD10 expression in cancer cells. In addition, stromal fibroblasts also showed varying amounts of CD10 expression in 92 (60.9%) tumor samples. CD10 overexpression in cancer cells as well as in stromal fibroblasts was an independent poor prognostic factor in both overall survival and disease-free survival. CD10 could be a promising target for the treatment of ESCC.

Global dissociation of HuR-mRNA complexes promotes cell survival after ionizing radiation.

Ionizing radiation (IR) triggers adaptive changes in gene expression. Here, we show that survival after IR strongly depends on the checkpoint kinase Chk2 acting upon its substrate HuR, an RNA-binding protein that stabilizes and/or modulates the translation of target mRNAs. Microarray analysis showed that in human HCT116 colorectal carcinoma cells (WT), IR-activated Chk2 triggered the dissociation of virtually all of HuR-bound mRNAs, since IR did not dissociate HuR target mRNAs in Chk2-null (CHK2-/-) HCT116 cells. Accordingly, several HuR-interacting mRNAs encoding apoptosis- and proliferation-related proteins (TJP1, Mdm2, TP53BP2, Bax, K-Ras) dissociated from HuR in WT cells, but remained bound and showed altered post-transcriptional regulation in CHK2-/- cells. Use of HuR mutants that were not phosphorylatable by Chk2 (HuR(3A)) and HuR mutants mimicking constitutive phosphorylation by Chk2 (HuR(3D)) revealed that dissociation of HuR target transcripts enhanced cell survival. We propose that the release of HuR-bound mRNAs via an IR-Chk2-HuR regulatory axis improves cell outcome following IR.

Cobalt chloride induces neuronal differentiation of human mesenchymal stem cells through upregulation of microRNA-124a.

Human mesenchymal stem cells (hMSCs) are known to have the capacity to differentiate into various cell types, including neurons. To examine our hypothesis that miRNA was involved in neuronal differentiation of hMSCs, CoCl2, a hypoxia-mimicking agent was used to induce neuronal differentiation, which was assessed by determining the expression of neuronal markers such as nestin and Tuj1. Treatment of hMSCs with CoCl2 led to increased expression of miR-124a, a neuron-specific miRNA. HIF-1α silencing and JNK inhibition abolished CoCl2-induced miR-124a expression, suggesting that JNK and HIF-1α signals were required for the miR-124a expression induced by CoCl2 in hMSCs. Overexpression of miR-124a or CoCl2 treatment suppressed the expression of anti-neural proteins such as SCP1 and SOX9. Silencing of both SCP1 and SOX9 induced neuronal differentiation of hMSCs, indicating that suppression of miR-124a targets is important for CoCl2-induced neuronal differentiation of hMSCs. Knockdown of HIF-1α or inhibition of JNK restored the expression of SCP1 and SOX9 in CoCl2-treated cells. Inhibition of miR-124a blocked CoCl2-induced suppression of SCP1 and SOX9 and abolished CoCl2-induced neuronal differentiation of hMSCs. Taken together, we demonstrate that miR-124a is critically regulates CoCl2-induced neuronal differentiation of hMSCs by suppressing the expression of SCP1 and SOX9.

Van der Waals Colloidal Crystals.

A general guiding principle for colloidal crystallization is to tame the attractive enthalpy such that it slightly overwhelms the repulsive interaction. As-synthesized colloids are generally designed to retain a strong repulsive potential for the high stability of suspensions, encoding appropriate attractive potentials into colloids has been key to their crystallization. Despite the myriad of interparticle attractions for colloidal crystallization, the van der Waals (vdW) force remains unexplored. Here, it is shown that the implementation of gold cores into silica colloids and the resulting vdW force can reconfigure the pair potential well depth to the optimal range between -1 and -4 kBT at tens of nanometer-scale colloidal distances. As such, colloidal crystals with a distinct liquid gap can be formed, which is evidenced by photonic bandgap-based diffractive colorization.

Role of UPF1 in lncRNA-HEIH regulation for hepatocellular carcinoma therapy.

UPF1, a novel posttranscriptional regulator, regulates the abundance of transcripts, including long noncoding RNAs (lncRNAs), and thus plays an important role in cell homeostasis. In this study, we revealed that UPF1 regulates the abundance of hepatocellular carcinoma upregulated EZH2-associated lncRNA (lncRNA-HEIH) by binding the CG-rich motif, thereby regulating hepatocellular carcinoma (HCC) tumorigenesis. UPF1-bound lncRNA-HEIH was susceptible to degradation mediated by UPF1 phosphorylation via SMG1 and SMG5. According to analysis of RNA-seq and public data on patients with liver cancer, the expression of lncRNA-HEIH increased the levels of miR-194-5p targets and was inversely correlated with miR-194-5p expression in HCC patients. Furthermore, UPF1 depletion upregulated lncRNA-HEIH, which acts as a decoy of miR-194-5p that targets GNA13, thereby promoting GNA13 expression and HCC proliferation. The UPF1/lncRNA-HEIH/miR-194-5p/GNA13 regulatory axis is suggested to play a crucial role in cell progression and may be a suitable target for HCC therapy.

Ubiquitin-mediated proteolysis of HuR by heat shock.

The RNA-binding protein HuR regulates the stability and translation of numerous mRNAs encoding stress-response and proliferative proteins. Although its post-transcriptional influence has been linked primarily to its cytoplasmic translocation, here we report that moderate heat shock (HS) potently reduces HuR levels, thereby altering the expression of HuR target mRNAs. HS did not change HuR mRNA levels or de novo translation, but instead reduced HuR protein stability. Supporting the involvement of the ubiquitin-proteasome system in this process were results showing that (1) HuR was ubiquitinated in vitro and in intact cells, (2) proteasome inhibition increased HuR abundance after HS, and (3) the HuR kinase checkpoint kinase 2 protected against the loss of HuR by HS. Within a central, HS-labile approximately 110-amino-acid region, K182 was found to be essential for HuR ubiquitination and proteolysis as mutant HuR(K182R) was left virtually unubiquitinated and was refractory to HS-triggered degradation. Our findings reveal that HS transiently lowers HuR by proteolysis linked to K182 ubiquitination and that HuR reduction enhances cell survival following HS.