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Background: Clinical observations indicate a correlation between the gut microbiota and overactive bladder (OAB) symptoms. Nevertheless, the causal relationship and mechanisms between gut microbiota and OAB symptoms remain elusive. Methods: Two-sample Mendelian randomization (MR) analyses were performed to assess the association between gut microbiota and OAB symptoms, including urinary incontinence (UI). Data were obtained from the MiBioGen International Consortium genome-wide association studies (GWAS) dataset and the IEU GWAS database. The inverse variance weighted method was used as the primary approach in the MR analysis, with the weighted median, MR-Egger, and weighted mode methods as supplementary approaches. Sensitivity analyses were employed to assess potential violations of the MR assumptions. Results: Our analysis identified seven gut bacterial taxa with a causal relationship to OAB and nine gut bacterial taxa associated with UI. Genera Eubacteriumfissicatenumgroup, LachnospiraceaeNK4A136group, and Romboutsia were identified as protective factors against OAB, while genera Barnesiella, FamilyXIIIAD3011group, Odoribacter, and RuminococcaceaeUCG005 were associated with an increased risk of OAB. A higher abundance of the genus Coprococcus3, order Burkholderiales, and phylum Verrucomicrobia predicted a lower risk of UI. Conversely, the class Mollicutes, genus Ruminococcus gauvreauii group, order Mollicutes RF9, and phylum Firmicutes and Tenericutes were positively correlated with UI risk. The sensitivity analysis excluded the influence of potential heterogeneity and horizontal pleiotropy. Conclusion: This study revealed a causal relationship between gut microbiota and OAB symptoms, providing new insights and a theoretical foundation to identify biomarkers and therapeutic targets for patients with OAB symptoms.

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MicroRNA (miRNA), a type of non-coding RNA, is crucial for controlling gene expression. Among the various miRNA families, miR166 stands out as a highly conserved group found in both model and crop plants. It plays a key role in regulating a wide range of developmental and environmental responses. In this review, we explore the diverse sequences of MIR166s in major crops and discuss the important regulatory functions of miR166 in plant growth and stress responses. Additionally, we summarize how miR166 interacts with other miRNAs and highlight the potential for enhancing agronomic traits by manipulating the expression of miR166 and its targeted HD-ZIP III genes.

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Brace root architecture is a critical determinant of maize's stalk anchorage and nutrition uptake, influencing root lodging resistance, stress tolerance, and plant growth. To identify the key microRNAs (miRNAs) in control of maize brace root growth, we performed small RNA sequencing using brace root samples at emergence and growth stages. We focused on the genetic modulation of brace root development in maize through manipulation of miR390 and its downstream regulated auxin response factors (ARFs). In the present study, miR167, miR166, miR172, and miR390 were identified to be involved in maize brace root growth in inbred line B73. Utilizing short tandem target mimic (STTM) technology, we further developed maize lines with reduced miR390 expression and analyzed their root architecture compared to wild-type controls. Our findings show that STTM390 maize lines exhibit enhanced brace root length and increased whorl numbers. Gene expression analyses revealed that the suppression of miR390 leads to upregulation of its downstream regulated ARF genes, specifically ZmARF11 and ZmARF26, which may significantly alter root architecture. Additionally, loss-of-function mutants for ZmARF11 and ZmARF26 were characterized to further confirm the role of these genes in brace root growth. These results demonstrate that miR390, ZmARF11, and ZmARF26 play crucial roles in regulating maize brace root growth; the involved complicated molecular mechanisms need to be further explored. This study provides a genetic basis for breeding maize varieties with improved lodging resistance and adaptability to diverse agricultural environments.

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Various observational studies have examined the prevalence and determinants of erectile dysfunction (ED) in men with type 1 diabetes across different geographical areas. Nevertheless, a comprehensive systematic review and meta-analysis to consolidate the worldwide prevalence and risk factors remains lacking. Hence, the primary study objective was to perform an extensive systematic review and meta-analysis that specifically examined ED prevalence and determinants in men with type 1 diabetes. A thorough exploration was conducted by examining electronic databases, such as PubMed, Embase, and Web of Science. The general ED prevalence and a 95% confidence interval (CI) in men with type 1 diabetes were summarized. The relevant risk factors were analyzed by deriving a comprehensive odds ratio (OR) from merging the ORs using fixed- or random-effects models. The sources of heterogeneity were investigated using subgroup analyses and meta-regression. This systematic review and meta-analysis included 19 articles involving 3788 men with type 1 diabetes. The meta-analysis revealed that men with type 1 diabetes had a combined ED prevalence of 42.5% (95% CI: 34.3%-50.8%). This prevalence showed significant heterogeneity (I2 = 96.2%, P < 0.01). Meta-regression revealed that age (P = 0.016) and type 1 diabetes duration (P = 0.004) were significant causes of heterogeneity. Furthermore, the ED risk in men with type 1 diabetes was significantly influenced by age, type 1 diabetes duration, body mass index, glycated hemoglobin (HbA1c), retinopathy, and smoking habits (all P < 0.05). In summary, this systematic review and meta-analysis revealed a significant prevalence of ED in men with type 1 diabetes, highlighting the importance of clinicians addressing concerns regarding ED in this specific group of individuals.

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Colour change is an important event during fruit ripening in blueberry. It is well known that miR156/SPLs act as regulatory modules mediating anthocyanin biosynthesis and ethylene plays critical roles during colour change, but the intrinsic connections between the two pathways remain poorly understood. Previously, we demonstrated that blueberry VcMIR156a/VcSPL12 affects the accumulation of anthocyanins and chlorophylls in tomato and Arabidopsis. In this study, we first showed that VcMIR156a overexpression in blueberry led to enhanced anthocyanin biosynthesis, decreased chlorophyll accumulation, and, intriguingly, concomitant elevation in the expression of ethylene biosynthesis genes and the level of the ethylene precursor ACC. Conversely, VcSPL12 enhanced chlorophyll accumulation and suppressed anthocyanin biosynthesis and ACC synthesis in fruits. Moreover, the treatment with ethylene substitutes and inhibitors attenuated the effects of VcMIR156a and VcSPL12 on pigment accumulation. Protein-DNA interaction assays indicated that VcSPL12 could specifically bind to the promoters and inhibit the activities of the ethylene biosynthetic genes VcACS1 and VcACO6. Collectively, our results show that VcMIR156a/VcSPL12 alters ethylene production through targeting VcACS1 and VcACO6, therefore governing fruit colour change. Additionally, VcSPL12 may directly interact with the promoter region of the chlorophyll biosynthetic gene VcDVR, thereby activating its expression. These findings established an intrinsic connection between the miR156/SPL regulatory module and ethylene pathway.

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OBJECTIVE: Parathyroidectomy (PTX) is the conclusive therapy for primary hyperparathyroidism (PHPT), but its effect on the risk of urolithiasis is inconclusive. We comprehensively reviewed the currently available research to investigate the impact of PTX on the likelihood of urolithiasis among individuals suffering PHPT. METHODS: Internet-based articles in English language released on Cochrane, PubMed, Scopus, Web of knowledge, and Embase up to September, 2023 were comprehensively reviewed. Each publication in contrast to the incidence, occurrence, or recurrence of urolithiasis after PTX versus medical treatment in PHPT patients was included. The outcome with pooled relative risks (RRs) and corresponding 95% confidence intervals (CIs) was examined employing DerSimonian and Laird's model of random effects. To determine the range of the real effect size of a future study in 95% of all populations, a prediction interval (PI) was also established. RESULTS: Finally, ten studies involving 74,190 patients were included. Results from randomized-controlled trials (RCTs) and observational studies (OSs) both revealed that PTX did not substantially lessen the vulnerability of urolithiasis among individuals with PHPT (RCTs: pooled relative risk [RR] 0.42, 95%CI 0.13-1.41, p = 0.163; OSs: pooled RR 1.37, 95%CI 0.96 to 1.97, p = 0.084). The PI (RCT: 0.03 to 5.96; OSs: 0.44-4.20) containing 1.0 suggested the possibility of consistent results in future studies. Subgroup and sensitivity analyses supported the above findings, and no evidence showed publication bias. CONCLUSION: Our analysis from the available RCTs or OSs did not give adequate or exact proof that the average effect of PTX lowers the incidence of urolithiasis among PHPT persons based on the random-effects model. Future research shall take into account the common effect of PTX as well as the prerequisites of preventive stone procedures, which will further help us assess the effectiveness of PTX in reducing kidney calculus comorbidity and develop techniques to avoid stone sequelae in these individuals.

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Penile crural fractures caused by traumatic injuries are rare urological emergencies similar to urethral bulb injuries. This case report discusses the findings of a 59-year-old patient who presented to our emergency department 12 h after an electric bicycle accident. Clinical examination revealed an elevated body temperature, bruised perineal skin, tender penis, and swollen scrotum. Imaging confirmed a penile fracture at the bilateral crus of the penis without considerable urethral trauma. The patient underwent conservative treatment and was followed up on an outpatient basis for approximately three months. Consequently, the patient is relieved of penile pain, has regained erectile function, and reports a satisfactory sexual life. Moreover, this study discusses the efficacy of conservative treatment combined with outpatient follow-up in managing bilateral penile crural fractures.

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In recent years, numerous epidemiological studies have investigated the prevalence of female sexual dysfunction (FSD) in females with inflammatory bowel disease (IBD). However, a comprehensive systematic review with meta-analysis pooling their findings is lacking. This study aimed to determine the pooled prevalence estimates of FSD and its risk factors among females with IBD based on extensive research in electronic databases (PubMed, Embase, and Web of Science) from inception until April 1, 2023. The overall prevalence of FSD among females with IBD, along with its 95% confidence interval (CI), and subgroup-specific prevalence rates, were summarized. Sources of heterogeneity were identified through subgroup analyses and meta-regression. A total of 13 studies were included in this systematic review and meta-analysis. The pooled global prevalence of FSD among females with IBD was 61.4% (95% CI: 52.8-70.1%). Sensitivity analysis, which involved excluding individual studies, indicated no significant variation in the pooled prevalence, confirming the robustness of our results. Additionally, a significant risk factor for FSD among females with IBD was the quality of life (OR = 0.39, 95% CI: 0.19-0.79). In conclusion, our systematic review and meta-analysis revealed a high prevalence of FSD among females with IBD, which warrants attention from health organizations and clinical practitioners. Importantly, the quality of life was identified as a potential risk factor for FSD in this population. Nonetheless, future prospective cohort studies with a large sample size are warranted to confirm these findings.

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BACKGROUND: Several observational studies have explored the prevalence and predictors of female sexual dysfunction (FSD) among females with type 1 diabetes. However, no systematic review and meta-analysis of pooled data provide reliable estimates of FSD prevalence among females with type 1 diabetes. AIM: To investigate the global prevalence of FSD, analyze the association between FSD risk and type 1 diabetes, and evaluate the predictors of FSD among females with type 1 diabetes. METHODS: The study search of the present systematic review was conducted through the Wanfang Database, China National Knowledge Infrastructure, PubMed, and Embase from the inception date to February 28, 2023. Heterogeneity among the studies was analyzed with the Q and I2 tests. The sources of heterogeneity were detected through subgroup analyses and meta-regression. OUTCOMES: Outcomes included the pooled prevalence of FSD among females with type 1 diabetes, the association between FSD risk and type 1 diabetes, and the predictors of FSD among females with type 1 diabetes. RESULTS: The pooled prevalence of FSD among females with type 1 diabetes was 38.5% (95% CI, 32.1%-45.0%). The risk of FSD was higher in patients with type 1 diabetes than in healthy controls (odds ratio [OR], 3.77; 95% CI, 2.24-6.35). The significant predictors of FSD among females with type 1 diabetes were depression status (OR, 2.77; 95% CI, 1.29-5.93) and longer diabetes duration (OR, 1.19; 95% CI, 1.06-1.34). CLINICAL IMPLICATIONS: Females with type 1 diabetes had a significantly increased prevalence of FSD, indicating that clinicians should be concerned about FSD among females with type 1 diabetes. STRENGTHS AND LIMITATIONS: The strength of the present study is that it is the first systematic review and meta-analysis to investigate the global prevalence and predictors of FSD among females with type 1 diabetes. The limitation is that the results revealed significant heterogeneity after pooling the articles. CONCLUSIONS: The present systematic review and meta-analysis revealed that the overall prevalence of FSD among females with type 1 diabetes was 38.5%, demonstrating a significant association between FSD risk and type 1 diabetes among females. Furthermore, we found that the significant predictors for FSD among females with type 1 diabetes were depression and a longer duration of diabetes.

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RCF1 is a highly conserved DEAD-box RNA helicase found in yeast, plants, and mammals. Studies about the functions of RCF1 in plants are limited. Here, we uncovered the functions of RCF1 in Arabidopsis thaliana as a player in pri-miRNA processing and splicing, as well as in pre-mRNA splicing. A mutant with miRNA biogenesis defects was isolated, and the defect was traced to a recessive point mutation in RCF1 (rcf1-4). We show that RCF1 promotes D-body formation and facilitates the interaction between pri-miRNAs and HYL1. Finally, we show that intron-containing pri-miRNAs and pre-mRNAs exhibit a global splicing defect in rcf1-4. Together, this work uncovers roles for RCF1 in miRNA biogenesis and RNA splicing in Arabidopsis.

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MicroRNAs (miRNAs) are small non-coding RNA molecules that play a crucial role in gene regulation. They are produced through an enzyme-guided process called dicing and have an asymmetrical structure with two nucleotide overhangs at the 3' ends. Artificial microRNAs (amiRNAs or amiRs) are designed to mimic the structure of miRNAs and can be used to silence specific genes of interest. Traditionally, amiRNAs are designed based on an endogenous miRNA precursor with certain mismatches at specific positions to increase their efficiency. In this study, the authors modified the highly expressed miR168a in Arabidopsis thaliana by replacing the single miR168 stem-loop/duplex with tandem asymmetrical amiRNA duplexes that follow the statistical rules of miRNA secondary structures. These tandem amiRNA duplexes, called "two-hit" amiRNAs, were shown to have a higher efficiency in silencing GFP and endogenous PDS reporter genes compared to traditional "one-hit" amiRNAs. The authors also demonstrated the effectiveness of "two-hit" amiRNAs in silencing genes involved in miRNA, tasiRNA, and hormone signalling pathways, individually or in families. Importantly, "two-hit" amiRNAs were also able to over-express endogenous miRNAs for their functions. The authors compare "two-hit" amiRNA technology with CRISPR/Cas9 and provide a web-based amiRNA designer for easy design and wide application in plants and even animals.

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Heat stress (HS) adversely affects plant growth and productivity. The Class A1 HS transcription factors (HSFA1s) act as master regulators in the plant response to HS. However, how HSFA1-mediated transcriptional reprogramming is modulated during HS remains to be elucidated. Here, we report that a module formed by the microRNAs miR165 and miR166 and their target transcript, PHABULOSA (PHB), regulates HSFA1 at the transcriptional and translational levels to control plant HS responses. HS-triggered induction of MIR165/166 in Arabidopsis thaliana led to decreased expression of target genes including PHB. MIR165/166 overexpression lines and mutations in miR165/166 target genes enhanced HS tolerance, whereas miR165/166 knockdown lines and plants expressing a miR165/166-resistant form of PHB were sensitive to HS. PHB directly repressed the transcription of HSFA1s and globally modulated the expression of HS-responsive genes. PHB and HSFA1s share a common target gene, HSFA2, which is essential for activation of plant responses to HS. PHB physically interacted with HSFA1s and exerted an antagonistic effect on HSFA1 transcriptional activity. PHB and HSFA1s co-regulated transcriptome reprogramming upon HS. Together, these findings indicate that heat-triggered regulation of the miR165/166-PHB module controls HSFA1-mediated transcriptional reprogramming and plays a critical role during HS in Arabidopsis.

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Grain weight and quality are always determined by grain filling. Plant microRNAs have drawn attention as key targets for regulation of grain size and yield. However, the mechanisms that underlie grain size regulation remain largely unclear because of the complex networks that control this trait. Our earlier studies demonstrated that suppressed expression of miR167 (STTM/MIM167) substantially increased grain weight. In a field test, the yield increased up to 12.90%-21.94% because of a significantly enhanced grain filling rate. Here, biochemical and genetic analyses revealed the regulatory effects of miR159 on miR167 expression. Further analysis indicated that OsARF12 is the major mediator by which miR167 regulates rice grain filling. Overexpression of OsARF12 produced grain weight and grain filling phenotypes resembling those of STTM/MIM167 plants. Upon in-depth analysis, we found that OsARF12 activates OsCDKF;2 expression by directly binding to the TGTCGG motif in its promoter region. Flow cytometry analysis of young panicles from OsARF12-overexpressing plants and examination of cell number in cdkf;2 mutants verified that OsARF12 positively regulates grain filling and grain size by targeting OsCDKF;2. Moreover, RNA sequencing results suggested that the miR167-OsARF12 module is involved in the cell development process and hormone pathways. OsARF12-overexpressing plants and cdkf;2 mutants exhibited enhanced and reduced sensitivity to exogenous auxin and brassinosteroid (BR) treatment, confirming that targeting of OsCDKF;2 by OsARF12 mediates auxin and BR signaling. Our results reveal that the miR167-OsARF12 module works downstream of miR159 to regulate rice grain filling and grain size via OsCDKF;2 by controlling cell division and mediating auxin and BR signals.

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Standardized naming systems are essential to integrate and unify distinct research fields, and to link multi-species data within and across kingdoms. We conducted a comprehensive survey of cytoplasmic ribosomal proteins (CRPs) in the dicot model Arabidopsis thaliana and the monocot model rice, noting that the standardized naming system has not been widely adopted in the plant community. We generated a database linking the old classical names to their updated and compliant names. We also explored the sequences, molecular evolution, and structural and functional characteristics of all plant CRP families, emphasizing evolutionarily conserved and plant-specific features through cross-kingdom comparisons. Unlike fungal CRP paralogs that were mainly created by whole-genome duplication (WGD) or retroposition under a concerted evolution mode, plant CRP genes evolved primarily through both WGD and tandem duplications in a rapid birth-and-death process. We also provide a web-based resource (http://www.plantcrp.cn/) with the aim of sharing the latest knowledge on plant CRPs and facilitating the continued development of a standardized framework across the entire community.

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The MIR2118 family has undergone tremendous expansion in the grass lineage, in which the miRNA targets numerous noncoding PHAS loci to produce 21-nt phased small interfering RNAs (phasiRNAs) involved in male fertility. However, the evolutionary trajectory of the grass MIR2118 genes and the functions of phasiRNAs have not yet been fully elucidated. We conducted comparative genomic, molecular evolution, expression and parallel analysis of RNA ends (PARE) analyses of MIR2118 and the miR2118-mediated regulatory pathway in grasses, focusing on Oryza sativa. In total, 617 MIR2118 and eight MIR1859 novel members were identified. Phylogenetic analyses showed that grass MIR2118 genes form a distinct clade from the MIR482/2118 genes of nongrass species. We reconstructed hypothetical evolutionary histories of the grass MIR2118 clusters and its MIR1859 variants, and examined the polycistronic composition and the differential expression of the osa-MIR2118 clusters. PARE data showed that osa-miR2118 might also direct the cleavage of some protein-coding gene transcripts. Importantly, we found that PARE analysis is inherently prone to false-positive target predictions when a large number of small RNAs, such as phasiRNAs, are analysed. Our results revealed the evolution and diversification of the MIR2118 family, and provide new insights into the functions of phasiRNAs in the grasses.

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MicroRNAs (miRNAs) are a class of small noncoding RNAs that regulate gene expression at the post-transcriptional level. Extensive studies have revealed that miRNAs have critical functions in plant growth, development, and stress responses and may provide valuable genetic resources for plant breeding research. We herein reviewed the development, mechanisms, and characteristics of miRNA techniques while highlighting widely used approaches, namely, the short tandem target mimic (STTM) approach. We described STTM-based advances in plant science, especially in the model crop rice, and introduced the CRISPR-based transgene-free crop breeding. Finally, we discussed the challenges and unique opportunities related to combining STTM and CRISPR technology for crop improvement and agriculture.

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BACKGROUND: Human endogenous retrovirus-H long terminal repeat-associating protein 2 (HHLA2) is a member of B7 family, which is upregulated in multiple tumors. However, its exact functions in non-small cell lung cancer (NSCLC) have not been fully understood. This study aimed to investigate the biological roles of HHLA2 in human NSCLC and the relevant mechanisms. In addition, the effects of tumor cell-derived HHLA2 on tumor-associated macrophage (TAM) polarization were explored. METHODS: NSCLC cell growth, migration, and invasion were assessed by colony formation and modified Boyden chamber assays. Cell cycle and the CD163+ TAMs were examined by flow cytometry. A co-culture model of THP-1 macrophages and NSCLC cells was conducted to investigate the impacts of tumor cell-derived HHLA2 on THP-1 macrophage polarization. Moreover, a xenograft nude mouse model was established to explore the effects of HHLA2 on tumorigenesis in vivo. RESULTS: HHLA2 was upregulated in A549 and H1299 cells compared with the normal lung epithelial BEAS-2B cells. HHLA2 deficiency inhibited NSCLC cell proliferation, migration, invasion, and induced G0/G1 phase arrest partially via inhibiting EGFR/MAPK/ERK signaling pathway. Furthermore, HHLA2 knockdown inhibited M2 polarization of TAMs via downregulating IL-10. In addition, knockdown of HHLA2 inhibited tumor growth in vivo. CONCLUSION: HHLA2 downregulation inhibited NSCLC growth and TAM M2 polarization. HHLA2 may serve as a therapeutic target and promising prognostic biomarker in NSCLC.

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MicroRNAs are important regulators in plant developmental processes and stress responses. In this study, we generated a series of maize STTM166 transgenic plants. Knock-down of miR166 resulted in various morphological changes, including rolled leaves, enhanced abiotic stress resistance, inferior yield-related traits, vascular pattern and epidermis structures, tassel architecture, as well as abscisic acid (ABA) level elevation and indole acetic acid (IAA) level reduction in maize. To profile miR166 regulated genes, we performed RNA-seq and qRT-PCR analysis. A total of 178 differentially expressed genes (DEGs) were identified, including 118 up-regulated and 60 down-regulated genes. These DEGs were strongly enriched in cell and intercellular components, cell membrane system components, oxidoreductase activity, single organism metabolic process, carbohydrate metabolic process, and oxidation reduction process. These results indicated that miR166 plays important roles in auxin and ABA interaction in monocots, yet the specific mechanism may differ from dicots. The enhanced abiotic stress resistance is partly caused via rolling leaves, high ABA content, modulated vascular structure, and the potential changes of cell membrane structure. The inferior yield-related traits and late flowering are partly controlled by the decreased IAA content, the interplay of miR166 with other miRNAs and AGOs. Taken together, the present study uncovered novel functions of miR166 in maize, and provide insights on applying short tandem target mimics (STTM) technology in plant breeding.

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Prostate cancer (PCa), an epithelial malignancy that occurs in the prostate, is the second leading cause of cancer death worldwide. MicroRNAs (miRs/miRNAs) are reported to have important applications in the field of cancer diagnosis and treatment. The present study aimed to investigate the function of miRNA-122 in the chemoresistance of PCa cells and the underlying mechanism. Significantly decreased miR-122 and increased pyruvate kinase (PKM2) levels were observed in docetaxel-resistant PCa cells, and PKM2 was negatively correlated with miR-122. MiR-122 mimic transfection in docetaxel-resistant LNCaP cells significantly inhibited cell proliferation, promoted apoptosis and decreased glucose uptake and lactate production, which was counteracted by PKM2 overexpression. Inhibition of miR-122 in LNCaP cells had an opposite effect to miR-122 mimic transfection. In addition, miR-122 mimic transfection significantly increased the sensitivity of docetaxel-resistant LNCaP cells to docetaxel, while inhibition of miR-122 significantly decreased the sensitivity of LNCaP cells to docetaxel. Luciferase reporter assays showed that miR-122 regulated PKM2 expression by binding to the 3'-untranslated region of PKM2. The results suggest that upregulation of miR-122 could enhance docetaxel sensitivity, inhibit cell proliferation and promote apoptosis in PCa cells,possibly through the downregulation of its target protein PKM2.