NOD-like receptor NLRC5 promotes neuroinflammation and inhibits neuronal survival in Parkinson's disease models.

Parkinson's disease (PD) is mainly characterized by the progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and neuroinflammation mediated by overactivated microglia and astrocytes. NLRC5 (nucleotide-binding oligomerization domain-like receptor family caspase recruitment domain containing 5) has been reported to participate in various immune disorders, but its role in neurodegenerative diseases remains unclear. In the current study, we found that the expression of NLRC5 was increased in the nigrostriatal axis of mice with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP)-induced PD, as well as in primary astrocytes, microglia and neurons exposed to different neurotoxic stimuli. In an acute MPTP-induced PD model, NLRC5 deficiency significantly reduced dopaminergic system degeneration and ameliorated motor deficits and striatal inflammation. Furthermore, we found that NLRC5 deficiency decreased the expression of the proinflammatory genes IL-1ß, IL-6, TNF-α and COX2 in primary microglia and primary astrocytes treated with neuroinflammatory stimuli and reduced the inflammatory response in mixed glial cells in response to LPS treatment. Moreover, NLRC5 deficiency suppressed activation of the NF-κB and MAPK signaling pathways and enhanced the activation of AKT-GSK-3ß and AMPK signaling in mixed glial cells. Furthermore, NLRC5 deficiency increased the survival of primary neurons treated with MPP+ or conditioned medium from LPS-stimulated mixed glial cells and promoted activation of the NF-κB and AKT signaling pathways. Moreover, the mRNA expression of NLRC5 was decreased in the blood of PD patients compared to healthy subjects. Therefore, we suggest that NLRC5 promotes neuroinflammation and dopaminergic degeneration in PD and may serve as a marker of glial activation.

The intracerebroventricular injection of lipopolysaccharide may induce neurogenic detrusor overactivity symptoms in mice.

PURPOSE: We aimed to explore if the intracerebroventricular (i.c.v.) injection of lipopolysaccharide (LPS) was able to evoke the cognitive and locomotive impairment and detrusor overactivity (DO) symptoms in mice. METHODS: This study compared the bladder function of mice that received the i.c.v. injection of LPS or saline. Specifically, basal pressure (BP), threshold pressure (TP), micturition pressure (MP), bladder capacity (BC), micturition volume (MV), bladder compliance (COM), frequency of micturition (MF), detrusor overactive index (DOI), frequency of non-voiding contractions (FNVCs), and amplitude of non-voiding contractions (ANVCs) were assessed by cystometry. The spontaneous voiding spot assay (VSA) was exerted to further assess the micturition patterns of mice. The Morris water maze (MWM) and the open field test (OFT) were used to detect the cognition and locomotive behaviors, respectively. Hematoxylin and eosin staining was conducted to evaluate the changes in morphology and histology of mice. The extent of injury in the prefrontal cortex was tested by using Nissl staining. RESULTS: The LPS-treated mice exhibited evidently DO characterized by the increase of MF, FNVCs, ANVCs, and DOI and the decrease of BC. The VSA further suggested that LPS induced urinary frequency and urinary incontinence in mice. Furthermore, neither signs of bladder inflammation nor the damage of bladder smooth muscle and urothelium in LPS-exposed mice was observed. LPS induced deficits in spatial learning, memory, and locomotor activity in mice. Neuronal cells in the prefrontal cortex were obviously lost in the LPS-treated mice. CONCLUSIONS: Acute neuroinflammation induced the cognitive and locomotive impairment and the neurogenic overactive bladder (NOAB) symptoms in mice. This novel animal model may contribute to further study the mechanisms of NOAB in neurodegenerative patients and assess the novel therapeutic strategies in the future.

Neuroprotection by dihydrotestosterone in LPS-induced neuroinflammation.

Microglia-induced neuroinflammation plays a vital role in the etiology and progression of neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease and multiple sclerosis. The neuroprotective role of androgens, including testosterone and its metabolite dihydrotestosterone (DHT), has been increasingly demonstrated in these diseases, but few studies investigated the effects of androgen on neuroinflammation. This study investigated the role of DHT in lipopolysaccharide (LPS)-induced neuroinflammation, neuronal damage and behavioral dysfunction, as well as underlying mechanisms. We showed that DHT inhibited LPS-induced release of proinflammatory factors, including TNF-α, IL-1ß, IL-6; iNOS, COX-2, NO, and PGE2 in BV2 cells and primary microglia by suppressing the TLR4-mediated NF-κB and MAPK p38 signaling pathways, thus protecting SH-SY5Y neurons from inflammatory damage induced by activated microglia. In an LPS-induced neuroinflammation mouse model, endogenous DHT depletion by castration exacerbated inflammatory responses by upregulating the levels of TNF-α, IL-1ß, IL-6, iNOS, and COX-2 in the serum and brain by increasing the LR4-mediated NF-κB and MAPK pathway activation, but these effects were restored by exogenous DHT supplementation. Moreover, DHT also regulated the mRNA levels of the anti-inflammatory cytokines IL-10 and IL-13 in the brain. In addition, DHT modulated the expression of Aß, the apoptotic proteins caspase-3, Bcl-2, and Bax, and synaptophysin, as well as neuronal damage in LPS-treated mouse brains. Further behavioral tests revealed that DHT ameliorated LPS-induced spatial and learning impairment and motor incoordination, and partly improved the locomotor activity in LPS-injected mice. Therefore, this study suggests that DHT exerts anti-neuroinflammatory and neuroprotective effects; thus, androgen replacement therapy is a potential therapeutic strategy for improving cognitive and behavioral function in neuroinflammation-related diseases.

Review of the Roles and Interaction of Androgen and Inflammation in Benign Prostatic Hyperplasia.

The lower urinary tract symptoms (LUTSs) and acute urinary retention (AUR) caused by benign prostatic hyperplasia (BPH) can seriously affect the quality of life of elderly men. Studies suggest that both androgens and inflammation greatly influence the occurrence and development of BPH in most patients. These two factors combined can also affect each other, leading to pathological changes in the stromal and epithelial tissue of the prostate transition zone in BPH patients. DHT in the prostate tissue of BPH patients may activate a chronic inflammatory response in the prostate, amplifying the expression of inflammatory factors and upregulating the proliferation ability of prostate tissue.

[Genetic diagnosis for a pedigree affected with hereditary nephrogenic diabetes insipidus].

OBJECTIVE: To explore the genetic basis for pedigree affected with hereditary nephrogenic diabetes insipidus (HNDI). METHODS: Next generation sequencing (NGS) with an osteology system gene panel was carried out for the proband. Suspected mutation was validated by Sanger sequencing of two relatives with similar symptoms and two unaffected relatives from the pedigree. RESULTS: The proband was found to carry a c.856C>T mutation of the AVPR2 gene. The same mutation was detected in the two relatives with similar symptoms and one unaffected healthy relative. CONCLUSION: The HNDI in this pedigree may be attributed to the c.856C>T mutation of the AVPR2 gene.

[Clinical trial of sexual dysfunctions in male patients with pituitary adenomas].

OBJECTIVE: To explore the clinical features and related factors of sexual dysfunctions in male patients with pituitary adenomas. METHODS: The questionnaires of sexual functions were collected from 86 male patients with pituitary adenomas. We examined the clinical features of sexual dysfunctions and analyzed the correlations between sexual behaviors and age, tumor type, invasiveness, tumor size, serum levels of prolactin (PRL) and testosterone. RESULTS: The incidence of sexual dysfunctions was 80.2% (69/86). Sexual dysfunctions were found in 84.6% (66/78) of the patients with functioning pituitary adenomas and 37.5% (3/8) of those with non-functioning pituitary adenoma respectively. In the PRL group, the incidence of erectile dysfunctions was 92.1% (35/38) and it was higher than those in the FSH (follicle-stimulating hormone) and GH (growth hormone) groups (P < 0.05). In the FSH group, the incidence of reduced sexual desire was 78.3% (18/23). In the GH group, the incidence of erectile dysfunctions was 70.6% (12/17) and the incidence of reduced sexual desire or ejaculation dysfunction was lower than that of the PRL/FSH group (P < 0.05). CONCLUSION: The incidence of sexual dysfunctions is quite high in males with pituitary adenomas, especially for those with functioning pituitary adenomas. The clinical features of sexual dysfunctions vary in different types of functioning pituitary adenoma. The incidence of erectile dysfunctions is the highest in the PRL group. Pathological type of pituitary tumors is a major risk factor of sexual dysfunctions.

[Lower urinary tract symptoms and prostatic growth pattern among old and middle-aged males in Shanghai community].

OBJECTIVE: To investigate the prevalence of lower urinary tract symptoms (LUTS) and the age-related growth pattern of the prostate among 40 -70 year-old males in Shanghai community. METHODS: Using cluster and stratified random sampling and IPSS, we investigated the prevalence of LUTS among 1000 males aged 40 -70 years in the general population of Shanghai from November 2009 to June 2010. We measured the transverse, anteroposterior and vertical diameters of the prostate and its transition zone in each volunteer by transrectal ultrasonography and established the equation for the age-related growth pattern of the prostate. RESULTS: In the 40 to 49-, 50 to 59- and 60 to 70-year groups, the incidence rates of moderate and severe LUTS (IPSS > or = 8) were 10.0%, 15.0% and 28.7%, respectively. The length, width, height and volume of the prostate and its transition zone were positively corrected with age (P < 0.05). The prostatic growth pattern equations based on the parameters of the transverse, anteroposterior and vertical diameters were Y = 1.6 x 10(-5)X3-0.002 1X2 + 0.074 6X + 0.677 2, Y = -2.4 x 10(-5)X3 + 0.003 3X2-0.1312X + 1.269, and Y = 1.6 x 10(-5)X3-0.001 8X2 + 0.073X- 0.690 9, respectively. The transverse and anteroposterior diameters of the prostate grew at a relatively similar rate, while the transverse diameter grew obviously faster than the vertical diameter before 60 years old, but the latter significantly increased and even exceeded the former after 60 years old. CONCLUSION: The prevalence of LUTS among old and middle-aged males in Shanghai community is similar to that recently reported at home and abroad. The transverse and anteroposterior diameters of the prostate grow at a relatively similar rate, but the vertical diameter increases faster after 60 years old.

Combined treatment with dihydrotestosterone and lipopolysaccharide modulates prostate homeostasis by upregulating TNF-α from M1 macrophages and promotes proliferation of prostate stromal cells.

Androgens and chronic inflammation, which play essential roles in the development of benign prostatic hyperplasia (BPH), are considered to be important factors in disorders of prostate homeostasis. These two factors may lead to pathological hyperplasia in the prostate transition zone of patients with BPH. However, few studies have examined the mechanism of how dihydrotestosterone (DHT) affects chronic inflammation in prostate tissue during the progression of BPH. This study examined the performance of DHT in lipopolysaccharide-treated M1 macrophages and the subsequent effects on the proliferation of prostate stromal and epithelial cells. We found that DHT increased secretion of the pro-inflammatory factor tumor necrosis factor (TNF)-α from M1 macrophages differentiated from THP-1 cells. The supernatant of M1 macrophages promoted the proliferation of WPMY-1 prostate stromal cells by upregulating B-cell lymphoma-extra large (Bcl-xL) and cellular Myc (c-Myc) levels by activating TNF-α-mediated nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways. Moreover, this supernatant increased the expression of androgen receptor in WPMY-1 cells, which was TNF-α-independent. Additionally, TNF-α protein expression was significantly higher in patients with BPH and a large prostate volume than that in those with a small prostate volume. Further analysis showed that higher serum testosterone combined with prostate-specific androgen concentrations was related to TNF-α expression. This study suggests that DHT modulates the inflammatory environment of BPH by increasing TNF-α expression from lipopolysaccharide-treated M1 macrophages and promotes the proliferation of prostate stromal cells. Targeting TNF-α, but not DHT, may be a promising strategy for patients with BPH.

High glucose and palmitic acid induces neuronal senescence by NRSF/REST elevation and the subsequent mTOR-related autophagy suppression.

Cell senescence is a basic aging mechanism. Previous studies have found that the cellular senescence in adipose tissue and other tissues, such as the pancreas, muscle and liver, is associated with the pathogenesis and progression of type 2 diabetes; however, strong evidence of whether diabetes directly causes neuronal senescence in the brain is still lacking. In this study, we constructed a high glucose and palmitic acid (HGP) environment on PC12 neuronal cells and primary mouse cortical neurons to simulate diabetes. Our results showed that after HGP exposure, neurons exhibited obvious senescence-like phenotypes, including increased NRSF/REST level, mTOR activation and cell autophagy suppression. Downregulation of NRSF/REST could remarkably alleviate p16, p21 and γH2A.X upregulations induced by HGP treatment, and enhance mTOR-autophagy of neurons. Our results suggested that the diabetic condition could directly induce neuronal senescence, which is mediated by the upregulation of NRSF/REST and subsequent reduction of mTOR-autophagy.

Safety and Effectiveness of Dapoxetine On Demand in Chinese Men With Premature Ejaculation: Results of a Multicenter, Prospective, Open-Label Phase IV Study.

INTRODUCTION: Dapoxetine on demand has been approved for premature ejaculation (PE) management in China; however, studies on the efficacy and safety of this treatment in the Chinese population are scarce. AIM: The aim of this study was to evaluate the safety and effectiveness of dapoxetine 30 mg and 60 mg on demand in Chinese men with PE. METHODS: Phase IV real-world study on 1,252 patients with PE. If men reported no response to dapoxetine 30 mg after 4 weeks treatment, dapoxetine has been uptitrated at 60 mg for 4 weeks more. MAIN OUTCOME MEASURE: Self-reported data were collected for demographics, general and sexual health characteristics, PE severity, and treatment safety and effectiveness, as measured by the PE profile questionnaire. RESULTS: Adverse events (AEs), such as nausea, thirst, headache, and dizziness, similarly to previous literature, were detected. The treatment-emergent AEs rate was higher in the patients treated with 30 and 60 mg (n = 192) compared with those treated with the dapoxetine 30 mg only (n = 1060) (34.4% vs 15.8%, respectively). No new safety concerns were observed. The overall effectiveness rates were 88.2% in subjects using 30 mg of dapoxetine, whereas a rescue from the previous failure was in 55.7% in the patients who received 60 mg after the initial 30 mg. Overall, 83.2% responded to dapoxetine at dosages equal to or lower than 60 mg. CONCLUSION: The results in this study demonstrated in a large Chinese population that on-demand dapoxetine is a safe and effective symptomatic treatment in patients with PE. J Peng, L Yang, L Liu, et al. Safety and Effectiveness of Dapoxetine On Demand in Chinese Men With Premature Ejaculation: Results of a Multicenter, Prospective, Open-Label Phase IV Study. Sex Med 2021;9:100296.

Increased expression of the heterogeneous nuclear ribonucleoprotein K in pancreatic cancer and its association with the mutant p53.

The heterogeneous nuclear ribonucleoprotein (hnRNP) K is an essential RNA and DNA binding protein involved in gene expression and signal transduction including DNA transcription, RNA splicing, RNA stability and translation. The role of hnRNP K in cancer is relatively understudied. However, several cellular functions strongly indicate that hnRNP K is involved in tumorigenesis. In this study, we investigated the altered protein expression and the subcellular distribution of the hnRNP K protein using tissue microarrays in pancreatic cancer. We showed an increased cytoplasmic hnRNP K in pancreatic cancer. This increase in hnRNP K protein occurs at the posttranscriptional level. We postulate that the cytoplasmic accumulation of hnRNP K will lead to silenced mRNA translation of tumor suppressor genes and thus contributes to pancreatic cancer development. We also demonstrated that knocking down of hnRNP K expression by siRNA inhibited pancreatic cancer cell growth and colony formation. hnRNP K was identified as a member of the p53/HDM2 pathway. Whether hnRNP K interacts with the mutant p53 is not known. Using two different pancreatic cancer cell lines, we can demonstrate that hnRNP K interacts with the mutant p53. The subcellular distribution and function of the mutant p53 and the interaction of hnRNP K/mutant p53 were affected by the Ras/MEK/ERK pathway, growth factors and the specific p53 mutations in pancreatic cancer cells. Since Kras is activated and p53 is mutated in most pancreatic cancers, these data unveiled an important new signaling pathway that linked by hnRNP K and mutant p53 in pancreatic cancer tumorigenesis.

Neuroprotection of dihydrotestosterone via suppression of the toll-like receptor 4/nuclear factor-kappa B signaling pathway in high glucose-induced BV-2 microglia inflammatory responses.

Hyperglycemia is considered to induce neuronal apoptosis via activating microglia inflammatory responses, thus involving in the development and progression of diabetic encephalopathy and neurodegenerative disorders. Increasing evidences suggest that androgen exerts neuroprotective functions including antiapoptosis, anti-inflammation and antioxidative stress. In this study, we investigate the anti-inflammatory role of dihydrotestosterone (DHT) in high glucose (HG)-induced neuroinflammatory response in BV-2 microglia. Our results revealed that DHT significantly inhibited HG-induced production of nitric oxide and prostaglandin E2 through suppressing the expression of corresponding regulatory enzymes - inducible NO synthase and cyclooxygenase-2. Also, DHT inhibited HG-induced expression of TNF-α and IL-1ß. Moreover, DHT suppressed the toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) signaling pathway. Furthermore, when SH-SY5Y neurons were cultured in HG-treated BV-2 microglial supernatant, DHT pretreatment significantly increased neuronal survival, indicating the neuroprotective role of DHT. Collectively, these results suggest that DHT could protect SH-SY5Y neurons from HG-mediated BV-2 microglia inflammatory damage through inhibiting TLR4/NF-κB signaling, suggesting that maintenance of androgen level in brain might have potential benefit in neurodegenerative diseases, especially in diabetes patients combined with cognitive disorders.

Urinary incontinence following deep brain stimulation of the globus pallidus internus: case report.

Deep brain stimulation (DBS) is a well-established therapy for patients with advanced Parkinson's disease (PD), dystonia, and other movement disorders. In contrast to the strong positive effects that have been documented for motor symptoms, the effects of DBS on nonmotor symptoms have not been fully elucidated. Some reports suggest that stimulation of the subthalamic nucleus may improve lower urinary tract symptoms in patients with PD; however, reports of the effects of globus pallidus internus (GPi) DBS on urinary symptoms are limited. The authors present the case of a 49-year-old woman with PD who developed severe urinary incontinence after 27 months of GPi DBS. The urinary incontinence disappeared when stimulation was turned off, and reemerged after it was turned on again. After activation of a more dorsal contact in the left electrode, the patient's urinary dynamics returned to normal.

Expression of miR-195 and MEK1 in patients with bladder cancer and their relationship to prognosis.

OBJECTIVE: MAPK kinase 1 (MEK1) plays an important role in regulating cell proliferation and apoptosis through activation of the ERK/MAPK signaling pathway. It was found that the expression of miR-195 in bladder cancer was abnormally decreased, suggesting that miR-195 may affect the development of bladder cancer. In this study, we examined the expression of miR-195 and MEK1 in bladder cancer tissues and analyzed the relationship between miR-195 and MEK1 in cell proliferation and apoptosis in bladder cancer cells. PATIENTS AND METHODS: The expression of MEK1 in bladder cancer tissues was detected by western blot, and the expression levels of miR-195 and MEK1 mRNA were detected by qRT-PCR. Log Rank test was used to compare the survival and prognosis of patients with low and high expression of miR-195 and MEK1 by using the median expression of miR-195 and MEK1. Bioinformatics analysis and double luciferase reporter gene test were used to verify the relationship between miR-195 and MEK1. Bladder cancer BIU-87 and 5637 cells were cultured in vitro and divided into two groups: miR-NC group and miR-195 mimic group. The expression of MEK1 and p-MEK1 protein was detected by western blot, apoptosis was detected by flow cytometry, and cell proliferation was detected by EdU staining. RESULTS: Compared with normal bladder tissue, expression of miR-195 in bladder cancer tissue was significantly decreased, while the expression of MEK1 mRNA and protein was significantly increased. The prognosis of patients with low expression of miR-195 was worse than those with high expression of miR-195. The prognosis of patients with low expression of MEK1 was better than those with high expression of MEK1. Bioinformatics analysis showed that there was a target complementary binding site between miR-195 and MEK1. Double luciferase reporter gene experiments confirmed that there was a target regulatory relationship between miR-195 and MEK1. miR-195 mimic transfection could significantly down-regulate the expression of MEK1 and p-MEK1 proteins in BIU-87 and 5637 cells, weaken cell proliferation, and increase cell apoptosis. CONCLUSION: Overexpression of miR-195 can inhibit the proliferation of bladder cancer cells by inhibiting MEK1, which provides further evidence for developing therapy against bladder cancer.

Identification of late-onset hypogonadism in middle-aged and elderly men from a community of China.

In this study, we investigated the essential criteria for late-onset hypogonadism (LOH) syndrome based on the presence of symptoms associated with low testosterone levels in Han Chinese men. Blood tests for total testosterone (TT) and sex hormone-binding globulin (SHBG) were performed, and the aging male symptoms (AMS) questionnaire was conducted in a randomly selected cohort composed of 944 Chinese men aged 40 to 79 years from nine urban communities. Three sexual symptoms (decreased ability/frequency of sexual activity, decreased number of morning erections, and decreased libido) were confirmed to be related to the total and free testosterone levels. The thresholds for TT were approximately 12.55 nmol l-1 for a decreased ability/frequency to perform sex, 12.55 nmol l-1 for decreased frequency of morning erections, and 14.35 nmol l-1 for decreased sexual desire. The calculated free testosterone (CFT) thresholds for these three sexual symptoms were 281.14, 264.90, and 287.21 pmol l-1 , respectively. TT <13.21 nmol l-1 (OR = 1.4, 95%CI: 1.0-1.9, P = 0.037) or CFT <268.89 pmol l-1 (OR = 1.5, 95%CI: 1.1-20, P = 0.020) was associated with an increase in the aforementioned three sexual symptoms. The prevalence of LOH was 9.1% under the criteria, including all three sexual symptoms with TT levels <13.21 nmol l-1 and CFT levels <268.89 pmol l-1 . Our results may improve the diagnostic accuracy of LOH in older men.

The HSP90 inhibitor 17-PAG effectively inhibits the proliferation and migration of androgen-independent prostate cancer cells.

Castration-resistant prostate cancer (CRPC) ultimately occurs after a period of treatment with androgen deprivation therapy. Furthermore, CRPC patients can only derive limited survival benefits from traditional cytotoxic drugs. HSP90, which is a molecular chaperone, plays a vital role in client protein processing and maintaining the function of cells. HSP90 is usually overexpressed in prostate cancer tissues, which makes it a potential target for managing prostate cancer. Geldanamycin (GA), which was recognized as the first natural HSP90 inhibitor, has demonstrated potent anti-tumor efficacy in large-scale pre-clinical studies, but its application in the clinic is not permitted due to its liver toxicity and unstable physical properties. In this study, we report a new GA derivative, 17-PAG (17-(propynylamino)-17-demethoxygeldanamycin), which demonstrates highly effective anti-tumor activity against androgen-independent prostate cancer cells. Treating cells with 17-PAG dose-dependently suppressed proliferation, reduced colony formation and induced apoptosis of DU-145/C4-2B cells. Moreover, 17-PAG suppressed the migration and invasion of DU-145/C4-2B cells by regulating epithelial mesenchymal transition (EMT). 17-PAG also downregulated the HSP90 client proteins, including Her2, EGFR, C-Raf, AKT, p-AKT, and CDK4. Animal assays confirmed that 17-PAG shows strong anti-tumor effects with no obvious organ toxicity in DU-145 cell xenografted nude mice. These results provide us with a potential target for treating androgen-independent prostate cancer in a safe and effective manner.

The tumor suppressive role of eIF3f and its function in translation inhibition and rRNA degradation.

Deregulated translation plays an important role in human cancer. We previously reported decreased eukaryotic initiation factor 3 subunit f (eIF3f) expression in pancreatic cancer. Whether decreased eIF3f expression can transform normal epithelial cells is not known. In our current study, we found evidence that stable knockdown of eIF3f in normal human pancreatic ductal epithelial cells increased cell size, nuclear pleomorphism, cytokinesis defects, cell proliferation, clonogenicity, apoptotic resistance, migration, and formation of 3-dimensional irregular masses. Our findings support the tumor suppressive role of eIF3f in pancreatic cancer. Mechanistically, we found that eIF3f inhibited both cap-dependent and cap-independent translation. An increase in the ribosomal RNA (rRNA) level was suggested to promote the generation of cancer. The regulatory mechanism of rRNA degradation in mammals is not well understood. We demonstrated here that eIF3f promotes rRNA degradation through direct interaction with heterogeneous nuclear ribonucleoprotein (hnRNP) K. We showed that hnRNP K is required for maintaining rRNA stability: under stress conditions, eIF3f dissociates hnRNP K from rRNA, thereby preventing it from protecting rRNA from degradation. We also demonstrated that rRNA degradation occurred in non-P body, non-stress granule cytoplasmic foci that contain eIF3f. Our findings established a new mechanism of rRNA decay regulation mediated by hnRNP K/eIF3f and suggest that the tumor suppressive function of eIF3f may link to impaired rRNA degradation and translation.