• Cancer
• Hallmarks
• LncRNA
• Long Non-coding RNA
• MIAT
• Oncogenic
• Solid malignancies

• Humans
• Colorectal Neoplasms/pathology
• Colorectal Neoplasms/microbiology
• Colorectal Neoplasms/metabolism
• Colorectal Neoplasms/drug therapy
• Fusobacterium nucleatum/physiology
• Fusobacterium nucleatum/pathogenicity
• Drug Resistance, Neoplasm
• Cell Proliferation
• Tumor Microenvironment
• Animals

• Ca2+‑activated Cl‑ channels
• TMEM16
• cancer
• coronavirus disease 19
• cystic fibrosis
• gene therapy

• Humans
• Phospholipid Transfer Proteins/metabolism
• Anoctamins/metabolism
• Anoctamins/genetics
• Animals
• Calcium/metabolism
• Chloride Channels/metabolism
• Neoplasms/drug therapy
• Neoplasms/metabolism
• COVID-19/metabolism
• SARS-CoV-2/metabolism
• Molecular Targeted Therapy
• Calcium Signaling/drug effects

• Humans
• TOR Serine-Threonine Kinases/metabolism
• Hypopharyngeal Neoplasms/pathology
• Hypopharyngeal Neoplasms/genetics
• Hypopharyngeal Neoplasms/metabolism
• Animals
• Autophagy
• Mice
• Cell Proliferation
• Signal Transduction
• Neoplasm Invasiveness
• Anoctamin-1/metabolism
• Anoctamin-1/genetics
• Cell Movement
• Neoplasm Proteins/genetics
• Neoplasm Proteins/metabolism
• Cell Line, Tumor
• Male
• Apoptosis
• Gene Expression Regulation, Neoplastic
• Squamous Cell Carcinoma of Head and Neck/pathology
• Squamous Cell Carcinoma of Head and Neck/metabolism
• Squamous Cell Carcinoma of Head and Neck/genetics
• Female
• Mice, Nude
• Xenograft Model Antitumor Assays
• Carcinoma, Squamous Cell/pathology
• Carcinoma, Squamous Cell/metabolism
• Carcinoma, Squamous Cell/genetics

• ZR2019PH113 Natural Science Foundation of Shandong Province
• ts20190991 Taishan Scholars Project
• 20230701677 Medical and Health Technology Project of Shandong Province

• Calcium
• Chloride channel
• Function
• Regulation
• Structure
• TMEM16A

• Humans
• Animals
• Anoctamin-1/metabolism
• Calcium/metabolism
• Chloride Channels/metabolism
• Ion Channel Gating

• MAPK/ERK pathway
• PI3K/Akt pathway
• colorectal cancer
• metformin
• microRNAs

• Established Research Grant Tour de Cure (Australia)

• ANO1
• HCC
• anoctamin 1
• chloride channels
• liver diseases

• Humans
• Anoctamin-1/metabolism
• Anoctamin-1/genetics
• Liver Diseases/metabolism
• Liver Diseases/pathology
• Liver Diseases/genetics
• Animals
• Signal Transduction
• Neoplasm Proteins/metabolism
• Neoplasm Proteins/genetics
• Liver Neoplasms/metabolism
• Liver Neoplasms/genetics
• Liver Neoplasms/pathology
• Carcinoma, Hepatocellular/metabolism
• Carcinoma, Hepatocellular/genetics
• Carcinoma, Hepatocellular/pathology
• Gene Expression Regulation

• Cancer immunity
• Colorectal cancer
• Epigenetic instability
• Genomic variation
• Lifestyle factor
• Metastasis cascade

• ANO1
• Activators
• Inhibitors
• Pharmacology
• Physiology
• TMEM16A

• Humans
• Chloride Channels/metabolism
• Anoctamin-1/metabolism
• Calcium/metabolism
• Binding Sites

• Cancer
• Drug target
• Expression mechanism
• Regulation mechanism
• TMEM16A

• Humans
• Ion Channels
• Neoplasms/drug therapy
• Neoplasms/genetics
• Signal Transduction
• Chloride Channels/genetics
• Chloride Channels/metabolism
• Carcinogenesis
• Calcium/metabolism

• DNA-damage repair
• HNPCC
• Lynch syndrome
• MSI
• colorectal cancer
• hereditary cancer
• hereditary non-polyposis colorectal cancer
• miRNAs
• microRNAs
• non-coding RNAs

• ESCRT
• Rab GTPases
• breast cancer
• colorectal cancer
• exosomal miRNA
• exosomes
• extracellular vesicles
• liver cancer
• noninvasive biomarkers
• prostate cancer

• DOG1
• GIST
• alimentary tract cancers
• antibody-drug conjugate
• liver metastasis

• fatty acid metabolism
• gut microbiome
• metabolite
• neoadjuvant chemoradiotherapy response
• rectal cancer

• artificial intelligence
• metastatic colorectal cancer
• ncRNA
• predictive biomarkers
• prognostic biomarkers

• Colorectal cancer
• SKAP1
• THUMPD3-AS1
• miR-218-5p

• Adenocarcinoma
• Cell Line, Tumor
• Cell Movement
• Cell Proliferation/genetics
• Colonic Neoplasms
• Colorectal Neoplasms/genetics
• Colorectal Neoplasms/pathology
• Gene Expression Regulation, Neoplastic
• Humans
• MicroRNAs/genetics
• MicroRNAs/metabolism
• Phosphoproteins/metabolism
• RNA, Long Noncoding/genetics

ANO1, a calcium-activated chloride channel (CACC), is also known as transmembrane protein 16A (TMEM16A). It plays a vital role in the occurrence, development, metastasis, proliferation, and apoptosis of various malignant tumors. This article reviews the mechanism of ANO1 involved in the replication, proliferation, invasion and apoptosis of various malignant tumors. Various molecules and Stimuli control the expression of ANO1, and the regulatory mechanism of ANO1 is different in tumor cells. To explore the mechanism of ANO1 overexpression and activation of tumor cells by studying the different effects of ANO1. Current studies have shown that ANO1 expression is controlled by 11q13 gene amplification and may also exert cell-specific effects through its interconnected protein network, phosphorylation of different kinases, and signaling pathways. At the same time, ANO1 also resists tumor apoptosis and promotes tumor immune escape. ANO1 can be used as a promising biomarker for detecting certain malignant tumors. Further studies on the channels and the mechanism of protein activity of ANO1 are needed. Finally, the latest inhibitors of ANO1 are summarized, which provides the research direction for the tumor-promoting mechanism of ANO1.

• ANO1
• cancer
• inhibitor
• miRNA
• protein network
• signal pathway
• tumor microenvironment

Transmembrane protein 16A (TMEM16A) forms a plasma membrane-localized Ca²⁺-activated Cl- channel. Its gene has been mapped to an area on chromosome 11q13, which is amplified in head and neck squamous cell carcinoma (HNSCC). In HNSCC, TMEM16A overexpression is associated with not only high tumor grade, metastasis, low survival, and poor prognosis, but also deterioration of clinical outcomes following platinum-based chemotherapy. Recent study revealed the interaction between TMEM16A and transforming growth factor-β (TGF-β) has an indirect crosstalk in clarifying the mechanism of TMEM16A-induced epithelial-mesenchymal transition. Moreover, human papillomavirus (HPV) infection can modulate TMEM16A expression along with epidermal growth factor receptor (EGFR), whose phosphorylation has been reported as a potential co-biomarker of HPV-positive cancers. Considering that EGFR forms a functional complex with TMEM16A and is a co-biomarker of HPV, there may be crosstalk between TMEM16A expression and HPV-induced HNSCC. EGFR activation can induce programmed death ligand 1 (PD-L1) synthesis via activation of the nuclear factor kappa B pathway and JAK/STAT3 pathway. Here, we describe an interplay among EGFR, PD-L1, and TMEM16A. Combination therapy using TMEM16A and PD-L1 inhibitors may improve the survival rate of HNSCC patients, especially those resistant to anti-EGFR inhibitor treatment. To the best of our knowledge, this is the first review to propose a biological validation that combines immune checkpoint inhibition with TMEM16A inhibition.

• Ca2+-activated Cl− channel
• EGFR
• HPV
• Head and neck squamous cell carcinoma
• Metastasis
• NF-kB
• PD-L1
• Proliferation
• STAT3
• TGF-β
• TMEM16A

• ANO1
• Diagnosis
• Drug target
• Marker
• Mechanism
• Prognosis
• Tumor

• Colorectal Neoplasms/genetics
• Colorectal Neoplasms/therapy
• Humans
• Liver Neoplasms/genetics
• Liver Neoplasms/therapy
• Tumor Microenvironment/genetics

Roles of chloride-associated transporters have been raised in various cancers. Although complicated ion movements, crosstalk among channels/transporters through homeostatic electric regulation, difficulties with experimental implementation such as activity measurement of intracellular location were disturbed to verify the precise modulation of channels/transporters, recently defined cancerous function and communication with tumor microenvironment of chloride channels/transporters should be highlighted beyond classical homeostatic ion balance. Chloride-associated transporters as membrane-associated components of chloride movement, regulations of transmembrane member 16A, calcium-activated chloride channel regulators, transmembrane member 206, chloride intracellular channels, voltage-gated chloride channels, cystic fibrosis transmembrane conductance regulator, voltage-dependent anion channel, volume-regulated anion channel, and chloride-bicarbonate exchangers are discussed.

The canonical roles of chloride channels and chloride-associated transporters have been physiologically determined; these roles include the maintenance of membrane potential, pH balance, and volume regulation and subsequent cellular functions such as autophagy and cellular proliferative processes. However, chloride channels/transporters also play other roles, beyond these classical function, in cancerous tissues and under specific conditions. Here, we focused on the chloride channel-associated cancers and present recent advances in understanding the environments of various types of cancer caused by the participation of many chloride channel or transporters families and discuss the challenges and potential targets for cancer treatment. The modulation of chloride channels/transporters might promote new aspect of cancer treatment strategies.

• chloride channels
• chloride-associated transporters
• metastasis
• migration and invasion
• prognostic marker

Over 90% of deaths in cancer patients are attributed to tumor drug resistance. Resistance to therapeutic agents can be due to an innate property of cancer cells or can be acquired during chemotherapy. In recent years, it has become increasingly clear that regulation of membrane ion channels is an important mechanism in the development of chemoresistance. Here, we review the contribution of ion channels in drug resistance of various types of cancers, evaluating their potential in clinical management. Several molecular mechanisms have been proposed, including evasion of apoptosis, cell cycle arrest, decreased drug accumulation in cancer cells, and activation of alternative escape pathways such as autophagy. Each of these mechanisms leads to a reduction of the therapeutic efficacy of administered drugs, causing more difficulty in cancer treatment. Thus, targeting ion channels might represent a good option for adjuvant therapies in order to counteract chemoresistance development.

• No funding was received for this article

• LncRNA MBNL1-AS1
• SOX4
• acute myocardial infarction
• cell apoptosis
• miR-132-3p

• 3' Untranslated Regions
• Animals
• Apoptosis
• Cell Line
• Cell Movement
• Cell Proliferation
• Creatine Kinase, MB Form/metabolism
• Disease Models, Animal
• MicroRNAs/genetics
• Myocardial Infarction/genetics
• Myocardial Infarction/metabolism
• Myocytes, Cardiac/cytology
• RNA, Long Noncoding/genetics
• Random Allocation
• Rats
• Rats, Wistar
• SOXC Transcription Factors/genetics
• Troponin I
• Up-Regulation

• Ca2+-activated Cl− channels
• Inflammation
• Pain
• Signaling
• TMEM16A

• Ca2+-activated Cl− channel
• TMEM16A
• anoctamin 1
• colorectal cancer
• honokiol

Anoctamin 1 (ANO1) or TMEM16A gene encodes a member of Ca²⁺ activated Cl^– channels (CaCCs) that are critical for physiological functions, such as epithelial secretion, smooth muscle contraction and sensory signal transduction. The attraction and interest in ANO1/TMEM16A arise from a decade long investigations that abnormal expression or dysfunction of ANO1 is involved in many pathological phenotypes and diseases, including asthma, neuropathic pain, hypertension and cancer. However, the lack of specific modulators of ANO1 has impeded the efforts to validate ANO1 as a therapeutic target. This review focuses on the recent progress made in understanding of the pathophysiological functions of CaCC ANO1 and the current modulators used as pharmacological tools, hopefully illustrating a broad spectrum of ANO1 channelopathy and a path forward for this target validation.

• ANO1
• ANO1, anoctamin-1
• ASM, airway smooth muscle
• Ang II, angiotensin II
• BBB, blood–brain barrier
• CAMK, Ca2+/calmodulin-dependent protein kinase
• CF, cystic fibrosis
• CFTR, cystic fibrosis transmembrane conductance regulator
• Ca2+-activated Cl– channels (CaCCs)
• CaCCinh-A01
• CaCCs, Ca2+ activated chloride channels
• Cancer
• Cystic fibrosis
• DRG, dorsal root ganglion
• Drug target
• EGFR, epidermal growth factor receptor
• ENaC, epithelial sodium channels
• ER, endoplasmic reticulum
• ESCC, esophageal squamous cell carcinoma
• FRT, fisher rat thyroid
• GI, gastrointestinal
• GIST, gastrointestinal stromal tumor
• GPCR, G-protein coupled receptor
• HNSCC, head and neck squamous cell carcinoma
• HTS, high-throughput screening
• ICC, interstitial cells of Cajal
• IPAH, idiopathic pulmonary arterial hypertension
• MAPK, mitogen-activated protein kinase
• NF-κB, nuclear factor κB
• PAH, pulmonary arterial hypertension
• PAR2, protease activated receptor 2
• PASMC, pulmonary artery smooth muscle cells
• PIP2, phosphatidylinositol 4,5-bisphosphate
• PKD, polycystic kidney disease
• T16Ainh-A01
• TGF-β, transforming growth factor-β
• TMEM16A
• VGCC, voltage gated calcium channel
• VRAC, volume regulated anion channel
• VSMC, vascular smooth muscle cells
• YFP, yellow fluorescent protein

• Ca2+-activated chloride channel
• Oral squamous cell carcinoma
• Simvastatin
• TMEM16A

We constructed a prognostic risk model for colon adenocarcinoma (COAD) using microRNAs (miRNAs) as biomarkers. Clinical data of patients with COADs and miRNA-seq data were from TCGA, and the differential expression of miRNAs (carcinoma vs. para-carcinoma tissues) was assessed using R software. COAD data were randomly divided into Training and Testing Sets. A linear prognostic risk model was constructed using Cox regression analysis based on the Training Set. Patients were classified as high-risk or low-risk according to the score of the prognostic model. Survival analysis and receiver operating characteristic (ROC) curves were used to evaluate model performance. The gene targets in the prognostic model were identified and their biological functions were analyzed. Analysis of COAD and normal cell lines using qPCR was used to verify the model. There were 134 up-regulated and 140 down-regulated miRNAs. We used the Training Set to develop a prognostic model based on the expression of seven miRNAs. ROC analysis indicated this model had acceptable prediction accuracy (area under the curve=0.784). Kaplan-Meier survival analysis showed that overall survival was worse in the high-risk group. Cox regression analysis showed that the 7-miRNA Risk Score was an independent prognostic factor. The 2,863 predicted target genes were mainly enriched in the MAPK, PI3K-AKT, proteoglycans in cancer, and mTOR signaling pathways. For unknown reasons, expression of these miRNAs in cancerous and normal cells differed somewhat from model predictions. Regardless, the 7-miRNA Risk Score can be used to predict COAD prognosis and may help to guide clinical treatment.

• The Cancer Genome Atlas (TCGA) database
• colon adenocarcinoma
• miRNA
• prognosis
• target genes

Circular RNAs (circRNAs) take part in colorectal cancer malignancies. CircRNA dedicator of cytokinesis 1 (circ_DOCK1) is involved in colorectal cancer progression, but the mechanism underlying this circRNA that takes part in colorectal cancer development remains largely undetermined.

Tumor and normal para-cancerous tissues were collected from 42 colorectal cancer patients. Human colorectal cancer cell lines (HCT116 and SW480) were used for the experiments in vitro. Circ_DOCK1, microRNA (miR)-132-3p, and ubiquitin-specific protease 11 (USP11) levels were measured through quantitative real-time polymerase chain reaction and Western blotting. Cell growth, metastasis, and apoptosis were investigated via colony formation, 5-ethynyl-2′-deoxyuridine (EdU) staining, MTT, flow cytometry, Western blotting, and transwell analyses. The target association was evaluated via dual-luciferase reporter analysis, RNA pull-down, and immunoprecipitation (RIP). Xenograft assay was performed using HCT116 cells. USP11 and Ki67 levels in tumor tissues were detected via immunohistochemistry.

Circ_DOCK1 expression was enhanced in colorectal cancer tissues and cells. Silencing circ_DOCK1 repressed cell growth, migration, and invasion, and facilitated apoptosis. Circ_DOCK1 sponged miR-132-3p, and miR-132-3p silence mitigated the effect of circ_DOCK1 interference on cell growth, metastasis, and apoptosis. MiR-132-3p targeted USP11, and circ_DOCK1 could regulate USP11 level by miR-132-3p. MiR-132-3p suppressed cell growth, metastasis, and apoptosis, and USP11 attenuated these effects. Knockdown of circ_DOCK1 decreased colorectal cancer cell xenograft tumor growth.

Circ_DOCK1 interference suppressed cell growth and metastasis, and increased apoptosis of colorectal cancer via decreasing USP11 by increasing miR-132-3p.

The online version contains supplementary material available at 10.1186/s12957-021-02173-x.

• Colorectal cancer
• USP11
• circ_DOCK1
• miR-132-3p

• Ca2+-activated chloride channels (CaCC)
• CaCC blockers/modulators
• CaCC molecular structure
• cell signaling pathways
• role of CaCC in pathophysiological processes
• role of CaCC in physiological processes

• TMEM16A
• biomarker
• cancer
• cancer therapy
• treatment

• Colorectal neoplasms
• MicroRNA
• Oncology
• Prognosis
• Systematic review

• Biomarkers, Tumor/metabolism
• Colorectal Neoplasms/genetics
• Colorectal Neoplasms/metabolism
• Colorectal Neoplasms/mortality
• Disease-Free Survival
• Gene Expression Regulation, Neoplastic/genetics
• Genes, Tumor Suppressor
• Humans
• Lymphatic Metastasis/genetics
• MicroRNAs/genetics
• MicroRNAs/metabolism
• Prognosis

Polycystic ovary syndrome (PCOS) is one of the most common endocrine metabolic disorders characterized by hyperandrogenism, polycystic ovaries and ovulatory dysfunction. Several studies have suggested that the aberrant expression of microRNAs (miRNAs/miRs) plays an important role in the pathogenesis of PCOS; however, the role and underlying mechanisms of miR-132 in the development of PCOS remain unclear. In the present study, the expression of miR-132 in granulosa cells (GCs) derived from 26 patients with PCOS and 30 healthy controls was detected by reverse transcription-quantitative PCR (RT-qPCR). The apoptosis of GCs was examined using a TUNEL assay. The human ovarian granulosa-like tumor cell line, KGN, was cultured for Cell Counting Kit-8 assays following the overexpression or knockdown of miR-132. TargetScan was applied to identify the potential targets of miR-132, which was further verified by a luciferase assay, RT-qPCR and western blotting. The expression of miR-132 was decreased in GCs from patients with PCOS. Moreover, the GCs of patients with PCOS exhibited significantly increased apoptotic nuclei. Furthermore, the overexpression of miR-132 inhibited the viability of KGN cells. In addition, the results verified that miR-132 directly targeted forkhead box protein A1 (Foxa1), the knockdown of which suppressed KGN cell viability. On the whole, the findings of the present study demonstrated that miR-132 inhibited cell viability and induced apoptosis by directly interacting with Foxa1. Thus, miR-132 may be a potential target for the treatment of patients with PCOS.

Anoctamin-1 (ANO1), also known as TMEM16A, is the most studied member of anoctamin family of calcium-activated chloride channels with diverse cellular functions. ANO1 controls multiple cell functions including cell proliferation, survival, migration, contraction, secretion, and neuronal excitation. This review summarizes the current knowledge of the cellular mechanisms governing the regulation of ANO1 expression and of ANO1-mediated intracellular signaling. This includes the stimuli and mechanisms controlling ANO1 expression, agonists and processes that activate ANO1, and signal transduction mediated by ANO1. The major conclusion is that this field is poorly understood, remains highly controversial, and requires extensive and rigorous further investigation.

• TMEM16A
• anoctamin-1
• calcium
• chloride
• signaling

• Akt/NF-κB
• Ca2+
• Carcinogenesis
• Metastasis
• Wnt/β-catenin
• pH

• Circular RNAs
• Colorectal cancer
• Liver metastasis
• Long non-coding RNA
• MicroRNAs
• Non-coding RNAs

• The Cancer Genome Atlas
• long non-coding RNAs
• overall survival
• prognosis

• Colorectal cancer
• chemoradiotherapy
• diagnosis
• microRNAs
• prognosis
• radiotherapy

• breast cancer
• microrna-152
• growth
• metastasis
• therapy
• rho-associated protein kinase 1 (rock1)

• 3' Untranslated Regions
• Breast Neoplasms/genetics
• Breast Neoplasms/metabolism
• Breast Neoplasms/pathology
• Cell Line, Tumor
• Cell Movement/genetics
• Cell Proliferation/genetics
• Down-Regulation/genetics
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• MCF-7 Cells
• MicroRNAs/genetics
• MicroRNAs/metabolism
• Neoplasm Invasiveness/genetics
• RNA, Neoplasm
• Real-Time Polymerase Chain Reaction
• rho-Associated Kinases/metabolism

• Cancer
• Colorectal
• Colorectal cancer
• Epigenetics
• Gut
• Microbiota

: Chemotherapy failure derived from drug resistance is the most important reason causing the recurrence in colorectal cancer patients. Therefore, it is necessary to shed light on the mechanism of chemotherapy resistance in colorectal cancer patients.

: We looked into the contribution of Fusobacterium nucleatum and ANO1 to chemoresistance in the human colorectal carcinoma cell lines. We silence and overexpress ANO1 in HCT116 and HT29 cells with lentivirus and siRNA knockdown technique in the absence or presence of F. nucleatum, oxaliplatin or 5-fluorouracil (5-FU). ANO1, p-pg, cleaved PARP, cleaved caspase-3, and EGFR expression was measured by Western blot. Cell apoptosis was measured by flow cytometry.

: We found that F. nucleatum promoted ANO1 expression on colon cancer cells. Moreover, ANO1 prevent colon cancer apoptosis from oxaliplatin and 5-FU. Additionally, knockdown ANO1 expression could block F. nucleatum protective effects and increase the apoptosis effects induced by oxaliplatin and 5-FU. Therefore, F. nucleatum might be biologically involved in the development of colon cancer chemoresistance via ANO1 pathway.

: Taken together, our findings provide a valuable insight into clinical management and therapy, which may ameliorate colorectal cancer patient outcomes.

• 5-fluorouracil
• ANO1
• F. nucleatum
• chemoresistance
• colorectal cancer
• oxaliplatin

Some new treatment methods have been explored to delay the recurrence of colorectal cancer (CRC). Early diagnosis plays an important role in the improvement of curative effect. The conventional methods used to diagnose and monitor CRC are fecal occult blood test (FOBT) and colonoscopy. However, FOBT has an unsatisfactory sensitivity, while colonoscopy is expensive and invasive. As new biomarkers, microRNAs, which can be detected in CRC tissues, cells, and body fluid as tumor suppressors or oncogenes, can be used in early diagnosis, the monitoring of metastasis and treatment, as well prognostic evaluation of CRC. This article reviews the diagnostic and prognostic value of microRNAs in CRC.

• MicroRNAs
• Colorectal cancer
• Diagnosis
• Metastasis
• Prognosis

• Clinical targets
• Colorectal cancer
• Esophageal cancer
• Gastric cancer
• Gastrointestinal cancer
• Hepatocellular carcinoma
• Ion channels
• Novel therapies
• Pancreatic cancer
• Prognostic biomarker

• Animals
• Antineoplastic Agents/pharmacology
• Antineoplastic Agents/therapeutic use
• Carcinogenesis/drug effects
• Carcinogenesis/pathology
• Disease Models, Animal
• Disease Progression
• Disease-Free Survival
• Down-Regulation
• Gastrointestinal Neoplasms/drug therapy
• Gastrointestinal Neoplasms/mortality
• Gastrointestinal Neoplasms/pathology
• Humans
• Ion Channels/antagonists & inhibitors
• Ion Channels/metabolism
• Up-Regulation

• R15 CA195061 NCI NIH HHS

• Anoctamin-1
• Calcium-activated chloride channels
• Cancer
• TMEM16A

• Animals
• Anoctamin-1/genetics
• Anoctamin-1/metabolism
• Biomarkers/metabolism
• Carcinogenesis/genetics
• Gene Expression Regulation, Neoplastic
• Humans
• Ion Channels/metabolism
• Neoplasms/diagnosis
• Neoplasms/metabolism
• Prognosis
• Signal Transduction

• R01 CA185039 NCI NIH HHS
• R01 NS069229 NINDS NIH HHS
• Howard Hughes Medical Institute

Background and aim: Increasing evidence shows that microRNAs play an important regulatory role in the development of several types of cancers. However, the role of microRNA-132 (miR-132) in human bladder cancer (BC) metastasis remains unclear. In this research, we aimed to investigate the effect of miR-132 on the cell migration and relate potential mechanism in BC.

Methods: miR-132 expression level was assessed by quantitative real-time PCR (qRT-PCR) in 32 BC tissues and BC cell lines (T24). The function of miR-132 was evaluated by Transwell assay. Gene expression was determined by using qRT-PCR or Western blot.

Results: The results showed that miR-132 had a lower expression in BC tissues than in adjacent normal tissues. At the same time, compared to human normal urethral epithelium cells, the expression level of miR-132 was downregulated in T24 cell lines. miR-132 overexpression significantly inhibited migration and invasion capacities in T24 cells, while downregulation of miR-132 expression strengthened such capacities. Compared with those transfected with miR-132 mimic, EMT-related markers and TGFβ1/Smad2 expression levels were higher in T24 cells transfected with miR-132 inhibitor. Moreover, EMT-related markers and Smad2 expression levels was obviously increased in BC tissues compared to the adjacent normal tissues. The correlation result indicated that the expression of miR-132 and Smad2 was reversed.

Conclusion: In short, our results suggest that miR-132 may play a suppressive role in the metastasis of BC cells via TGFβ1/Smad2 signaling pathway.

• epithelial-mesenchymal transition
• human bladder cancer
• metastasis
• microRNA-132

• Anoctamin 1
• Epidermal growth factor
• Estrogen receptor
• Tamoxifen