3D Printed Porous Zirconia Biomaterials based on Triply Periodic Minimal Surfaces Promote Osseointegration In Vitro by Regulating Osteoimmunomodulation and Osteo/Angiogenesis.

The triply periodic minimal surface (TPMS) is a highly useful structure for bone tissue engineering owing to its nearly nonexistent average surface curvature, high surface area-to-volume ratio, and exceptional mechanical energy absorption properties. However, limited literature is available regarding bionic zirconia implants using the TPMS structure for bone regeneration. Herein, we employed the digital light processing (DLP) technology to fabricate four types of zirconia-based TPMS structures: P-cell, S14, IWP, and Gyroid. For cell proliferation, the four porous TPMS structures outperformed the solid zirconia group (P-cell > S14 > Gyroid > IWP > ZrO2). In vitro assessments on the biological responses and osteogenic properties of the distinct porous surfaces identified the IWP and Gyroid structures as promising candidates for future clinical applications of porous zirconia implants because of their superior osteogenic capabilities (IWP > Gyroid > S14 > P-cell > ZrO2) and mechanical properties (ZrO2 > IWP > Gyroid > S14 > P-cell). Furthermore, the physical properties of the IWP/Gyroid surface had more substantial effects on bone immune regulation by reducing macrophage M1 phenotype polarization while increasing M2 phenotype polarization compared with the solid zirconia surface. Additionally, the IWP and Gyroid groups exhibited enhanced immune osteogenesis and angiogenesis abilities. Collectively, these findings highlight the substantial impact of topology on bone/angiogenesis and immune regulation in promoting bone integration.

CD56 polysialylation promotes the tumorigenesis and progression via the Hedgehog and Wnt/ß-catenin signaling pathways in clear cell renal cell carcinoma.

BACKGROUND: CD56 has been observed in malignant tumours exhibiting neuronal or neuroendocrine differentiation, such as breast cancer, small-cell lung cancer, and neuroblastoma. Abnormal glycosylation modifications are thought to play a role in regulating tumour cell proliferation, migration, and invasion. Nevertheless, the exact roles and molecular mechanisms of CD56 and polysialylated CD56 (PSA-CD56) in the development and progression of clear cell renal cell carcinoma (ccRCC) remain elusive. Here we unveil the biological significance of CD56 and PSA-CD56 in ccRCC. METHODS: In this study, we employed various techniques, including immunohistochemistry (IHC), RT-qPCR, and western blot, to examine the mRNA and protein expression levels in both human ccRCC tissue and cell lines. Lentivirus infection and CRISPR/Cas9 system were utilized to generate overexpression and knockout cell lines of CD56. Additionally, we conducted several functional assays, such as CCK-8, colony formation, cell scratch, and transwell assays to evaluate cell growth, proliferation, migration, and invasion. Furthermore, we established a xenograft tumor model to investigate the role of CD56 in ccRCC in vivo. To gain further insights into the molecular mechanisms associated with CD56, we employed the Hedgehog inhibitor JK184 and the ß-catenin inhibitor Prodigiosin. RESULTS: CD56 was significantly overexpressed in both human ccRCC tissues and renal cancer cell lines compared to adjacent normal tissues and normal renal epithelial cells. In vitro and in vivo experiments revealed that the knockout of CD56 inhibited the proliferation, migration, and invasion capabilities of ccRCC cells, whereas the overexpression of PSA-CD56 promoted these capacities. Finally, PSA-CD56 overexpression was found to activate both the Hedgehog and Wnt/ß-catenin signaling pathways. CONCLUSION: Our findings demonstrate that the oncogenic function of CD56 polysialylation plays a vital role in the tumorigenesis and progression of ccRCC, implying that targeting PSA-CD56 might be a feasible treatment target for ccRCC.

Impact of Poly(Ester Amide) Structure on Properties and Drug Delivery for Prostate Cancer Therapy.

Objective: We aim to develop a polymer library consisting of phenylalanine-based poly(ester amide)s (Phe-PEAs) for cancer therapy and investigate the structure-property relationship of these polymers to understand their impact on the drug delivery efficiency of corresponding nanoparticles (NPs). Impact Statement: Our study provides insights into the structure-property relationship of polymers in NP-based drug delivery applications and offers a potential polymer library and NP platform for enhancing cancer therapy. Introduction: Polymer NP-based drug delivery systems have demonstrated substantial potential in cancer therapy by improving drug efficacy and minimizing systemic toxicity. However, successful design and optimization of these systems require a comprehensive understanding of the relationship between polymer structure and physicochemical properties, which directly influence the drug delivery efficiency of the corresponding NPs. Methods: A series of Phe-PEAs with tunable structures was synthesized by varying the length of the methylene group in the diol part of the polymers. Subsequently, Phe-PEAs were formulated into NPs for doxorubicin (DOX) delivery in prostate cancer therapy. Results: Small adjustments in polymer structure induced the changes in the hydrophobicity and thermal properties of the PEAs, consequently NP size, drug loading capacity, cellular uptake efficacy, and cytotoxicity. Additionally, DOX-loaded Phe-PEA NPs demonstrated enhanced tumor suppression and reduced side effects in prostate tumor-bearing mice. Conclusion: Phe-PEAs, with their finely tunable structures, show great promise as effective and customizable nanocarriers for cancer therapy.

Multiple Origins and Genomic Basis of Complex Traits in Sighthounds.

Sighthounds, a distinctive group of hounds comprising numerous breeds, have their origins rooted in ancient artificial selection of dogs. In this study, we performed genome sequencing for 123 sighthounds, including one breed from Africa, six breeds from Europe, two breeds from Russia, and four breeds and 12 village dogs from the Middle East. We gathered public genome data of five sighthounds and 98 other dogs as well as 31 gray wolves to pinpoint the origin and genes influencing the morphology of the sighthound genome. Population genomic analysis suggested that sighthounds originated from native dogs independently and were comprehensively admixed among breeds, supporting the multiple origins hypothesis of sighthounds. An additional 67 published ancient wolf genomes were added for gene flow detection. Results showed dramatic admixture of ancient wolves in African sighthounds, even more than with modern wolves. Whole-genome scan analysis identified 17 positively selected genes (PSGs) in the African population, 27 PSGs in the European population, and 54 PSGs in the Middle Eastern population. None of the PSGs overlapped in the three populations. Pooled PSGs of the three populations were significantly enriched in "regulation of release of sequestered calcium ion into cytosol" (gene ontology: 0051279), which is related to blood circulation and heart contraction. In addition, ESR1, JAK2, ADRB1, PRKCE, and CAMK2D were under positive selection in all three selected groups. This suggests that different PSGs in the same pathway contributed to the similar phenotype of sighthounds. We identified an ESR1 mutation (chr1: g.42,177,149 T > C) in the transcription factor (TF) binding site of Stat5a and a JAK2 mutation (chr1: g.93,277,007 T > A) in the TF binding site of Sox5. Functional experiments confirmed that the ESR1 and JAK2 mutation reduced their expression. Our results provide new insights into the domestication history and genomic basis of sighthounds.

A robust gene prognostic index composed of GZMB, IRF1, and TP63 can stratify the risk of two metastatic urothelial carcinoma cohorts based on immune checkpoint blockade therapy.

BACKGROUND: Immune checkpoint blockade (ICB) therapy has become a first-line treatment option for metastatic urothelial carcinoma (mUC) patients who do not meet the criteria of cisplatin. Still, only a few people can benefit from it, so useful predictive markers are needed. METHODS: Download the ICB-based mUC and chemotherapy-based bladder cancer cohorts, and extract the expression data of pyroptosis-related genes (PRG). The LASSO algorithm was used to construct the PRG prognostic index (PRGPI) in the mUC cohort, and we verified the prognostic ability of PRGPI in two mUC and two bladder cancer cohorts. RESULTS: Most of the PRG in the mUC cohort were immune-activated genes, and a few were immunosuppressive genes. The PRGPI composed of GZMB, IRF1, and TP63 can stratify the risk of mUC. In IMvigor210 and GSE176307 cohorts, the P-values of Kaplan Meier analysis was < 0.01 and 0.002, respectively. PRGPI could also predict ICB response, and the chi-square test of the two cohorts had P-values of 0.002 and 0.046, respectively. In addition, PRGPI can also predict the prognosis of two bladder cancer cohorts without ICB therapy. The PRGPI and the expression of PDCD1/CD274 had a high degree of synergistic correlation. The Low PRGPI group showed prominent characteristics of immune infiltration and was enriched in the immune signal activation pathway. CONCLUSION: The PRGPI we constructed can effectively predict the treatment response and overall survival rate of mUC patients treated with ICB. The PRGPI can help mUC patients achieve individualized and accurate treatment in the future.

Screening of Rosemary Essential Oils with Different Phytochemicals for Antioxidant Capacity, Keratinocyte Cytotoxicity, and Anti-Proliferative Activity.

Nowadays, the demand for rosemary essential oils (REOs) in the cosmetic, food, and pharmaceutical industries is increasing, and the abundant germplasm resources of rosemary provide more possibilities for functional applications. The REOs from six cultivars were selected to evaluate and compare their bioactivities. REOs have good cellular antioxidant activity in scavenging reactive oxygen species, and the technology for order preference by similarity to an ideal solution (TOPSIS)-random forest multivariate model indicated that 'Dutch Mill' REO has the best antioxidant activity, which is closely related to its verbenone content. In addition, α-pinene-dominant REOs are more toxic to human keratinocytes, which is closely related to the content of α-pinene, as revealed by multivariate analyses. Moreover, anti-proliferative assays on six cancer cell lines showed that all REOs have a higher anti-proliferative ability against human pancreatic cancer cell line SW1990 and gastric epithelial cell line NCI-N87. Among them, 'Miss Jessopp's Upright' and 'Blue Lagoon' REOs exhibit more prominent anti-proliferative activity. Our study provides a reference value for exploring the application potential of different REOs by evaluating their differences in chemical composition and bioactivity.

Application of synthetic biology in bladder cancer.

ABSTRACT: Bladder cancer (BC) is the most common malignant tumor of the genitourinary system. The age of individuals diagnosed with BC tends to decrease in recent years. A variety of standard therapeutic options are available for the clinical management of BC, but limitations exist. It is difficult to surgically eliminate small lesions, while radiation and chemotherapy damage normal tissues, leading to severe side effects. Therefore, new approaches are required to improve the efficacy and specificity of BC treatment. Synthetic biology is a field emerging in the last decade that refers to biological elements, devices, and materials that are artificially synthesized according to users' needs. In this review, we discuss how to utilize genetic elements to regulate BC-related gene expression periodically and quantitatively to inhibit the initiation and progression of BC. In addition, the design and construction of gene circuits to distinguish cancer cells from normal cells to kill the former but spare the latter are elaborated. Then, we introduce the development of genetically modified T cells for targeted attacks on BC. Finally, synthetic nanomaterials specializing in detecting and killing BC cells are detailed. This review aims to describe the innovative details of the clinical diagnosis and treatment of BC from the perspective of synthetic biology.

Intratumoral fibrosis and patterns of immune infiltration in clear cell renal cell carcinoma.

BACKGROUND: Intratumoral fibrosis was positively correlated with histological grade of renal clear cell carcinoma (ccRCC) and intratumoral inflammation. However, the association of intratumoral fibrosis with the immune infiltration of ccRCC was few evaluated. METHODS: We used the second harmonic generation (SHG)-based imaging technology and evaluated the intratumoral fibrosis in ccRCC, and then divided the patients into the high fibrosis group (HF) and the low fibrosis group (LF). Meanwhile, the Kaplan-Meier survival curve analysis was performed to analyze the relationship between intratumoral fibrosis and the disease-free survival rate. Antibody arrays were used for seeking difference in cytokines and immune infiltration between the HF group (N = 11) and LF group (N = 11). The selected immune infiltration marker was then verified by immunohistochemistry (IHC) staining in 45 ccRCC samples. RESULTS: Out of 640 cytokines and immune infiltration markers, we identified 115 proteins that were significantly different in quantity between ccRCC and adjacent normal tissues. In addition, the Venn diagram indicated that six proteins, including Cytotoxic T-Lymphocyte Associated Protein 4 (CTLA4), were significantly associated with intratumoral fibrosis (p < 0.05). The GO/KEGG enrichment analysis indicated that the proteins associated with intratumoral fibrosis were involved in the immunity and tumor-infiltrating lymphocytes. The expression of the CTLA4 was negatively correlated with collagen level, confirmed by IHC staining of CTLA4 (p < 0.05). CONCLUSIONS: The study indicated that the intratumoral fibrosis level was negatively correlated with the expression of CTLA4 in the tumor immune microenvironment of the ccRCC, which posed the potential value of targeting the stroma of the tumor, a supplement to immunotherapy. However, the specific mechanism of this association is still unclear and needs further investigation.

Gemcitabine-Resistant Biomarkers in Bladder Cancer are Associated with Tumor-Immune Microenvironment.

To identify key biomarkers in gemcitabine (GEM)-resistant bladder cancer (BCa) and investigate their associations with tumor-infiltrating immune cells in a tumor immune microenvironment, we performed the present study on the basis of large-scale sequencing data. Expression profiles from the Gene Expression Omnibus GSE77883 dataset and The Cancer Genome Atlas BLCA dataset were analyzed. Both BCa development and GEM-resistance were identified to be immune-related through evaluating tumor-infiltrating immune cells. Eighty-two DEGs were obtained to be related to GEM-resistance. Functional enrichment analysis demonstrated they were related to regulation of immune cells proliferation. Protein-protein interaction network selected six key genes (CAV1, COL6A2, FABP4, FBLN1, PCOLCE, and CSPG4). Immunohistochemistry confirmed the down-regulation of the six key genes in BCa. Survival analyses revealed the six key genes were significantly associated with BCa overall survival. Correlation analyses revealed the six key genes had high infiltration of most immune cells. Gene set enrichment analysis further detected the key genes might regulate GEM-resistance through immune response and drug metabolism of cytochrome P450. Next, microRNA-gene regulatory network identified three key microRNAs (hsa-miR-124-3p, hsa-miR-26b-5p, and hsa-miR-192-5p) involved in GEM-resistant BCa. Connectivity Map analysis identified histone deacetylase inhibitors might circumvent GEM-resistance. In conclusion, CAV1, COL6A2, FABP4, FBLN1, PCOLCE, and CSPG4 were identified to be critical biomarkers through regulating the immune cell infiltration in an immune microenvironment of GEM-resistance and could act as promising treatment targets for GEM-resistant muscle-invasive BCa.

Prepubertal-type teratoma in a postpubertal patient: case report and review of literature.

Prepubertal-type teratomas are rare, especially in postpubertal patients. We present a case of a 43-year-old man with a palpable painless mass in the left-sided testis discovered by accident. Scrotal ultrasound and magnetic resonance imaging revealed a 2.7×2.0 cm mass inside the left testis, and malignancy could not be excluded, though classical serum tumor makers were within normal limits. Radical testicular resection was then conducted, and the pathologic report proved the mass to be a testicular epidermoid cyst, a rare form of prepubertal-type teratoma. Relevant published literature is also reviewed in our text.

LincRNA-p21 suppresses glutamine catabolism and bladder cancer cell growth through inhibiting glutaminase expression.

Long intergenic non-coding RNA p21 (lincRNA-p21) is down-regulated in some solid tumors. Glutamine catabolism plays an important role in cancer development. However, the role of lincRNA-p21 and its association with glutamine catabolism remain unknown in bladder cancer (BC). In the present study, we investigated the involvement of lincRNA-p21 and glutamine catabolism in BC cell growth and found that ectopic linRNA-p21 expression reduced the proliferation and growth of BIU87 and 5637 cells. Opposite results were observed in lincRNA-p21 silenced J82 and T24 cells. The expression of glutaminase (GLS), intracellular level of glutamate and α-Ketoglutarate (α-KG) were negatively regulated by lincRNA-p21. GLS overexpression reversed the suppressive function of lincRNA-p21 on BC cell growth and proliferation. In contrast, GLS reduction by siRNA blunted the viability of lincRNA-p21 lowly expressed BC cells. Furthermore, lincRNA-p21 and GLS abundance dictated the sensitivity of BC cells to bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl)ethyl sulfide (BPTES) treatment. Importantly, reduced lincRNA-p21 expression and increased GLS mRNA level were observed in BC tissues compared with the normal tissues. Our results demonstrate that lincRNA-p21 suppresses the BC cell growth through inhibiting GLS and glutamine catabolism. Targeting this cascade may be a promising treatment strategy for BC patients.

A revolutionary tool: CRISPR technology plays an important role in construction of intelligentized gene circuits.

With the development of synthetic biology, synthetic gene circuits have shown great applied potential in medicine, biology, and as commodity chemicals. An ultimate challenge in the construction of gene circuits is the lack of effective, programmable, secure and sequence-specific gene editing tools. The clustered regularly interspaced short palindromic repeat (CRISPR) system, a CRISPR-associated RNA-guided endonuclease Cas9 (CRISPR-associated protein 9)-targeted genome editing tool, has recently been applied in engineering gene circuits for its unique properties-operability, high efficiency and programmability. The traditional single-targeted therapy cannot effectively distinguish tumour cells from normal cells, and gene therapy for single targets has poor anti-tumour effects, which severely limits the application of gene therapy. Currently, the design of gene circuits using tumour-specific targets based on CRISPR/Cas systems provides a new way for precision cancer therapy. Hence, the application of intelligentized gene circuits based on CRISPR technology effectively guarantees the safety, efficiency and specificity of cancer therapy. Here, we assessed the use of synthetic gene circuits and if the CRISPR system could be used, especially artificial switch-inducible Cas9, to more effectively target and treat tumour cells. Moreover, we also discussed recent advances, prospectives and underlying challenges in CRISPR-based gene circuit development.

Lentivirus-mediated shRNA targeting MUTYH inhibits malignant phenotypes of bladder cancer SW780 cells.

OBJECTIVES: MUTYH is a protein-coding gene that takes part in base excision repair. Many previous studies have reported that MUTYH is directly related to hereditary adenomatous polyposis and colorectal cancer and is also associated with other cancers. However, the relationship between MUTYH and bladder cancer (BC) is unknown. MATERIALS AND METHODS: The expression of MUTYH and clinical characteristics of BC were collected from databases including The Cancer Genome Atlas and Cancer Cell Line Encyclopedia. RNA sequencing and quantitative real-time PCR were used to detect MUTYH expression in SW780 BC cells. The level of MUTYH was stably downregulated by lentivirus-mediated vector in SW780 cells. Cell proliferation was evaluated using Cell Counting Kit-8 assay and 5-ethynyl-20-deoxyuridine assay, migration was detected using scratch assay and Transwell assay, and apoptosis was determined using ELISA. RESULTS: MUTYH was upregulated in BC tissues and SW780 cells and its expression level was positively associated with the stage and grade of carcinomas. MUTYH was successfully downregulated in SW780 cells by transducing with a lentivirus-mediated shRNA targeting MUTYH. MUTYH knockdown inhibited the proliferation and migration and induced apoptosis in SW780 cells. CONCLUSION: Our data suggest that MUTYH is a new participant in bladder urothelial carcinoma. MUTYH may play a role as a biomarker and therapeutic target in BC.

Oestrogen promotes tumorigenesis of bladder cancer by inducing the enhancer RNA-eGREB1.

In recent years, studies have shown that enhancer RNAs (eRNAs) can be transcribed from enhancers. Increasing evidence has revealed that eRNAs play critical roles in the development of various cancers. Oestrogen-associated eRNAs are closely related to breast cancer. In view of the gender differences in bladder cancer (BCa), we suppose that oestrogen-associated eRNAs are also involved in tumorigenesis of BCa. In our study, we first demonstrated that eGREB1 derived from the enhancer of an oestrogen-responsive gene-GREB1 was up-regulated in BCa tissues, and the expression level of eGREB1 is positively associated with the histological grade and TNM stage of BCa. Knockdown of eGREB1 by CRISPR-Cas13a could inhibit cell proliferation, migration and invasion and induce apoptosis in BCa cells T24 and 5637. Besides, we exhibited the promoting effect of oestrogen on BCa cells. What's more, down-regulation of eGREB1 could improve the malignant biological characteristics of BCa cells induced by oestrogen. In conclusion, our data indicated that eGREB1 plays oncogenic role and oestrogen may promote the occurrence and progression of BCa by inducing eGREB1 production. Our findings provide new insights into the prevention of BCa and develop a novel therapeutic target for the treatment of BCa.

Enhancer RNA - P2RY2e induced by estrogen promotes malignant behaviors of bladder cancer.

Enhancers are transcriptional regulatory elements that increase target gene expression. It has reported that enhancers could universally transcribe into enhancer RNAs (eRNAs) with stimulation. Increasing evidence showed eRNAs participated in various disease processes including malignant tumors. P2RY2 enhancer RNA (P2RY2e) is an estrogen-responsive eRNA and involved in the development of breast cancer. However, the relationship between P2RY2e and bladder cancer (BCa) is unclear. In the study, we discovered that P2RY2e was upregulated in BCa tissues and estrogen-treated cells. Estrogen promoted the malignant abilities of BCa cells. P2RY2e knockdown by CRISPR-Cas13a inhibit the cell multiplication, invasion and migration. Additionally, the cell apoptosis was facilitated. What's more, downregulation of P2RY2e could weaken the cancer-promoting effects of estrogen on BCa. Our study revealed that P2RY2e played a carcinogenic role in BCa and estrogen might promote the initiation of BCa by inducing P2RY2e. We provide a potential therapeutic target for BCa and a new perspective for the tumorigenesis of bladder cancer.

Enhancer RNAs (eRNAs): New Insights into Gene Transcription and Disease Treatment.

Enhancers are cis-acting elements that have the ability to increase the expression of target genes. Recent studies have shown that enhancers can act as transcriptional units for the production of enhancer RNAs (eRNAs), which are hallmarks of activity enhancers and are involved in the regulation of gene transcription. The in-depth study of eRNAs is of great significance for us to better understand enhancer function and transcriptional regulation in various diseases. Therefore, eRNAs may be a potential therapeutic target for diseases. Here, we review the current knowledge of the characteristics of eRNAs, the molecular mechanisms of eRNAs action, as well as diseases related to dysregulation of eRNAs.

High expression of enhancer RNA MARC1 or its activation by DHT is associated with the malignant behavior in bladder cancer.

Enhancer RNAs (eRNAs), a subclass of noncoding RNA from enhancers, have biological functions in gene expression. However, their potential role in bladder cancer (BCa) remains largely unknown. The present study investigated the functional role of androgen-associated androgen receptor (AR) mediated-eRNA MARC1 (eMARC1) in BCa progression. Cell proliferation, migration, and apoptosis of BCa cell lines (5637 and T24) with different eMARC1 expression levels or treated with 5α-dehydrotestosterone (DHT) were investigated. In the current study, we discovered that eMARC1 was highly expressed in BCa tissues and cell lines, and eMARC1 overexpression promoted the progression of BCa cells, while knockdown of eMARC1 suppressed tumorigenesis. DHT treatment significantly elevated eMARC1 expression levels, which also facilitated cell proliferation, motility, and inhibited cell apoptosis. We further found that eMARC1 silencing impaired the androgenic effect of DHT in BCa cells. These results suggested that eMARC1 exerted its effects on BCa cell progression, and DHT promoted bladder cancer progression by activating eMARC1.

Current Advances on the Important Roles of Enhancer RNAs in Gene Regulation and Cancer.

Revealing the gene regulation networks governing cancer initiation and development is necessary while it remains uncompleted. In recent years, enhancers have been reported to be widely transcribed, resulting in the generation of enhancer RNAs (eRNAs). Previous studies have reported that eRNAs are a subclass of long noncoding RNAs (lncRNAs), which play a critical role in gene regulation and cancer development. These eRNAs can promote enhancer-promoter (E-P) looping formation by binding to other protein factors or propel expression of downstream protein-coding gene. In this review, we have focused on the characteristics of eRNAs and illustrated the biological function and potential mechanism of eRNAs in regulating gene expression and cancer development.

Synthetic artificial "long non-coding RNAs" targeting oncogenic microRNAs and transcriptional factors inhibit malignant phenotypes of bladder cancer cells.

Both oncogenic transcription factors (TFs) and microRNAs (miRNAs) play important roles in human cancers, acting as transcriptional and post-transcriptional regulators, respectively. These phenomena raise questions about the ability of an artificial device to simultaneously regulate miRNAs and TFs. In this study, we aimed to construct artificial long non-coding RNAs, "alncRNAs", and to investigate their therapeutic effects on bladder cancer cell lines. Based on engineering principles of synthetic biology, we combined tandem arrayed aptamer cDNA sequences for TFs with tandem arrayed cDNA copies of binding sites for the miRNAs to construct alncRNAs. In order to prove the utility of this platform, we chose ß-catenin and the miR-183-182-96 cluster as the functional targets and used the bladder cancer cell lines 5637 and SW780 as the test models. Dual-luciferase reporter assay, real-time quantitative PCR (qRT-PCR) and related phenotypic experiments were used to test the expression of related genes and the therapeutic effects of our devices. The result of dual-luciferase reporter assay and qRT-PCR showed that alncRNAs could inhibit transcriptional activity of TFs and expression of corresponding microRNAs. Using functional experiments, we observed decreased cell proliferation, increased apoptosis, and motility inhibition in alncRNA-infected bladder cancer cells. What's more, follow-up mechanism experiments further confirmed the anti-tumor effect of our devices. In summary, our synthetic devices indeed function as anti-tumor regulators, which synchronously accomplish transcriptional and post-transcriptional regulation in bladder cancer cells. Most importantly, anti-cancer effects were induced by the synthetic alncRNAs in the bladder cancer lines. Our devices, all in all, provided a novel strategy and methodology for cancer studies, and might show a great potential for cancer therapy if the challenges of in vivo DNA delivery are overcome.