TAF1 is needed for the proliferation and maturation of thyroid follicle cells via Notch signaling.

Thyroid dysgenesis (TD) is the common pathogenic mechanism of congenital hypothyroidism (CH). In addition, known pathogenic genes are limited to those that are directly involved in thyroid development. To identify additional candidate pathogenetic genes, we performed forward genetic screening for TD in zebrafish, followed by positional cloning. The candidate gene was confirmed in vitro using the Nthy-ori 3.1 cell line and in vivo using a zebrafish model organism. We obtained a novel zebrafish line with thyroid dysgenesis and identified the candidate pathogenetic mutation TATA-box binding protein associated Factor 1 (taf1) by positional cloning. Further molecular studies revealed that taf1 was needed for the proliferation of thyroid follicular cells by binding to the NOTCH1 promoter region. Knockdown of TAF1 impaired the proliferation and maturation of thyroid cells, thereby leading to thyroid dysplasia. This study showed that TAF1 promoted Notch signaling and that this association played a pivotal role in thyroid development.NEW & NOTEWORTHY In our study, we obtained a novel zebrafish line with thyroid dysgenesis (TD) and identified the candidate pathogenetic mutation TATA-box binding protein associated Factor 1 (taf1). Further researches revealed that taf1 was required for thyroid follicular cells by binding to the NOTCH1 promoter region. Our findings revealed a novel role of TAF1 in thyroid morphogenesis.

TSHR Variant Screening and Phenotype Analysis in 367 Chinese Patients With Congenital Hypothyroidism.

Background: Genetic defects in the human thyroid-stimulating hormone (TSH) receptor (TSHR) gene can cause congenital hypothyroidism (CH). However, the biological functions and comprehensive genotype-phenotype relationships for most TSHR variants associated with CH remain unexplored. We aimed to identify TSHR variants in Chinese patients with CH, analyze the functions of the variants, and explore the relationships between TSHR genotypes and clinical phenotypes. Methods: In total, 367 patients with CH were recruited for TSHR variant screening using whole-exome sequencing. The effects of the variants were evaluated by in-silico programs such as SIFT and polyphen2. Furthermore, these variants were transfected into 293T cells to detect their Gs/cyclic AMP and Gq/11 signaling activity. Results: Among the 367 patients with CH, 17 TSHR variants, including three novel variants, were identified in 45 patients, and 18 patients carried biallelic TSHR variants. In vitro experiments showed that 10 variants were associated with Gs/cyclic AMP and Gq/11 signaling pathway impairment to varying degrees. Patients with TSHR biallelic variants had lower serum TSH levels and higher free triiodothyronine and thyroxine levels at diagnosis than those with DUOX2 biallelic variants. Conclusions: We found a high frequency of TSHR variants in Chinese patients with CH (12.3%), and 4.9% of cases were caused by TSHR biallelic variants. Ten variants were identified as loss-of-function variants. The data suggest that the clinical phenotype of CH patients caused by TSHR biallelic variants is relatively mild. Our study expands the TSHR variant spectrum and provides further evidence for the elucidation of the genetic etiology of CH.

Radix Tetrastigma Hemsleyani Flavone represses cutaneous squamous cell carcinoma via Janus kinase/signal transducer and activator of transcription 3 pathway inactivation.

Cutaneous squamous cell carcinoma (CSCC) is the second most common malignant skin tumor and significantly affects patients' quality of life and health. The Janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3) pathway activation is involved in CSCC development. Radix Tetrastigma hemsleyani flavone (RTHF) is an active Radix Tetrastigma extract (RTE), which was recently reported to have promising inhibitory effects on CSCC. However, the underlying functional mechanisms of this inhibition remain unknown. In the present study, A431 cells or SCL-1 cells were incubated with 1, 5, and 10 mg/mL RTHF for 48 h, respectively. A significantly increased wound closure rate, decreased number of migrated and invaded cells, decreased colony number, and elevated apoptotic rate were observed after treatment with 1, 5, and 10 mg/mL RTHF. Furthermore, after incubation with RTHF, p-JAK1/JAK1, p-JAK2/JAK2, and p-STAT3/STAT3 levels were drastically reduced. An A431 xenograft model was constructed, followed by oral administration of 15, 30, or 60 mg/kg RTHF for 21 consecutive days. A significantly lower increase in tumor volume and reduced tumor weight were observed in all RTHF-treated groups. In addition, JAK/STAT3 signaling was drastically repressed in tumor tissues. Collectively, RTHF inhibited CSCC progression, which may be associated with JAK/STAT3 pathway inactivation.

The structure and function of olfactory receptors.

Olfactory receptors (ORs) form the most important chemosensory receptor family responsible for our sense of smell in the nasal olfactory epithelium. This receptor family belongs to the class A G protein-coupled receptors (GPCRs). Recent research has indicated that ORs are involved in many nonolfactory physiological processes in extranasal tissue, such as the brain, pancreas, and testes, and implies the possible role of their dysregulation in various diseases. The recently released structures of OR51E2 and consensus OR52 have also unveiled the uniqueness of ORs from other class A GPCR members. In this review, we discuss these recent developments and computational modeling efforts toward understanding the structural properties of unresolved ORs, which could guide potential future OR-targeted drug discovery.

Plant Polyphenols Attenuate DSS-induced Ulcerative Colitis in Mice via Antioxidation, Anti-inflammation and Microbiota Regulation.

The pathogenesis of ulcerative colitis (UC) is associated with inflammation, oxidative stress, and gut microbiota imbalance. Although most researchers have demonstrated the antioxidant bioactivity of the phenolic compounds in plants, their UC-curing ability and underlying mechanisms still need to be further and adequately explored. Herein, we studied the antioxidation-structure relationship of several common polyphenols in plants including gallic acid, proanthocyanidin, ellagic acid, and tannic acid. Furthermore, the in vivo effects of the plant polyphenols on C57BL/6 mice with dextran-sulfate-sodium-induced UC were evaluated and the action mechanisms were explored. Moreover, the interplay of several mechanisms was determined. The higher the number of phenolic hydroxyl groups, the stronger the antioxidant activity. All polyphenols markedly ameliorated the symptoms and pathological progression of UC in mice. Furthermore, inflammatory cytokine levels were decreased and the intestinal barrier was repaired. The process was regulated by the antioxidant-signaling pathway of nuclear-erythroid 2-related factor 2. Moreover, the diversity of the intestinal microbiota, Firmicutes-to-Bacteroides ratio, and relative abundance of beneficial bacteria were increased. An interplay was observed between microbiota regulation and oxidative stress, immunity, and inflammatory response. Furthermore, intestinal barrier repair was found to be correlated with inflammatory responses. Our study results can form a basis for comprehensively developing plant-polyphenol-related medicinal products.

Swertia bimaculata moderated liver damage in mice by regulating intestine microbiota.

Swertia bimaculata (SB) is a medicinal herb in China having an array of therapeutic and biological properties. This study aimed to explore the attenuating effect of SB on carbon tetrachloride (CCl4) induced hepato-toxicity by regulation of gut microbiome in ICR mice. For this purpose, CCl4 was injected intraperitoneally in different mice groups (B, C, D and E) every 4th day for a period of 47 days. Additionally, C, D, and E groups received a daily dose (50 mg/kg, 100 mg/kg, and 200 mg/kg respectively) of Ether extract of SB via gavage for the whole study period. The results of serum biochemistry analysis, ELISA, H&E staining, and sequencing of the gut microbiome, indicated that SB significantly alleviates the CCl4-induced liver damage and hepatocyte degeneration. The serum levels of alanine transaminase, aspartate aminotransferase, malondialdehyde, interleukin 1 beta and tumor necrosis factor-alpha were significantly lower in SB treated groups compared to control while levels of glutathione peroxidase were raised. Also, the sequencing data indicate that supplementation with SB could restore the microbiome and its function in CCl4-induced variations in intestinal microbiome of mice by significantly downregulating the abundances of pathogenic intestinal bacteria species including Bacteroides, Enterococcus, Eubacterium, Bifidobacterium while upregulating the levels of beneficial bacteria like Christensenella in the gut. In conclusion, we revealed that SB depicts a beneficial effect against hepatotoxicity induced by CCl4 in mice through the remission of hepatic inflammation and injury, through regulation of oxidative stress, and by restoring gut microbiota dysbiosis.

MIF is a critical regulator of mononuclear phagocytic infiltration in hepatocellular carcinoma.

Immunotherapy targeting tumor-associated macrophages (TAMs) is a promising approach to treating cancer. However, the limited drug targets and ambiguous mechanisms impede the development of clinical immunotherapy strategies. To elucidate the underlying processes involved in mononuclear phagocyte (MNP) infiltration and phenotypic changes in hepatocellular carcinoma (HCC), we integrated single-cell RNA-sequencing data from 100,030 cells derived from patients with HCC and healthy individuals and compared the phenotypes and origins of the MNPs in the tumor core, tumor periphery, adjacent normal tissue, and healthy liver samples. Using machine learning and multi-omics analyses, we identified 445 infiltration-associated genes and potential drug targets affecting this process. Through in vitro experiments, we found that the expression of macrophage migration inhibitory factor (MIF) is the upstream regulator of secreted phosphoprotein 1 (SPP1) and promote migration in TAMs. Our findings also indicate that MIF promotes tumor metastasis and invasion and is a promising potential target for treating HCC.

Novel NQO1 substrates bearing two nitrogen redox centers: Design, synthesis, molecular dynamics simulations, and antitumor evaluation.

By analyzing the crystal structure of NQO1, an additional binding region for the ligand was discovered. In this study, a series of derivatives with a novel skeleton bearing two nitrogen redox centers were designed by introducing amines or hydrazines to fit with the novel binding region of NQO1. Compound 24 with a (4-fluorophenyl)hydrazine substituent was identified as the most efficient substrate for NQO1 with the reduction rate and catalytic efficiency of 1972 ± 82 µmol NADPH/min/µmol NQO1 and 6.4 ± 0.4 × 106 M-1s-1, respectively. Molecular dynamics (MD) simulation revealed that the distances between the nitrogen atom of the redox centers and the key Tyr128 and Tyr126 residues were 3.5 Å (N1-Tyr128) and 3.4 Å (N2-Tyr126), respectively. Compound 24 (IC50/A549 = 0.69 ± 0.09 µM) showed potent antitumor activity against A549 cells both in vitro and in vivo through ROS generation via NQO1-mediated redox cycling, leading to a promising NQO1-targeting antitumor candidate.

Biocontrol yeast T-2 improves the postharvest disease resistance of grape by stimulation of the antioxidant system.

Table grapes are susceptible to external pathogens during postharvest storage. The resulting continuous oxidative stress causes damage and aging, thereby reducing the defense against disease. In this study, the effect of biocontrol yeast T-2 on the storage performance of grapes was evaluated. After T-2 treatment, the grapefruits rot rate and lesion diameter caused by Botrytis cinerea (B. cinerea) were significantly decreased at 2-5 days after inoculation (DAI). Additionally, the browning rate and shedding rate of grapefruit during storage were significantly reduced at 2-5 DAI, and the weight loss rate was significantly reduced at 3-5 DAI. The decreased malondialdehyde (MDA) content in grapefruits at 1-5 DAI with T-2 indicated a reduction in oxidative damage. Furthermore, the activities of antioxidant enzymes such as peroxidase (POD), catalase (CAT), phenylalanin ammonia-lyase (PAL) were significantly increased during most storage time after being treated with T-2. Moreover, the contents of total phenolics and flavonoids and the expression levels of key enzyme genes in metabolic pathways were increased after T-2 treatment during most postharvest storage time, providing evidence that T-2 changed the biological process of phenolic flavonoid metabolism. The increase in enzymatic and nonenzymatic antioxidants after treatment with T-2 reflected the strengthening of the antioxidant system, hence postponing fruit senescence and promoting storage performance under the stress of B. cinerea.

Effect and Mechanism of Pharmaceutical Excipients on Berberine to Alleviate Ulcerative Colitis via Regulating Gut Microbiota.

BACKGROUND: Various potential effect of drugs on alleviating diseases by regulating intestinal microbiome as well as the pharmaceutical excipients on gut microbiota has been revealed. However, the interaction between them is rarely investigated. METHODS: Histological analysis, immunohistochemistry analysis, enzyme-linked immunosorbent assay (ELISA) analysis, RT-qPCR, and 16S rRNA analysis were utilized to explore the effect mechanism of the five excipients including hydroxypropyl methylcellulose (HPMC) F4M, Eudragit (EU) S100, chitosan (CT), pectin (PT), and rheum officinale polysaccharide (DHP) on berberine (BBR) to cure UC. RESULTS: The combined BBR with PT and DHP group exhibited better therapeutic efficacy of UC with significantly increased colon length, and decreased hematoxylin-eosin (H&E) scores than other groups. Furthermore, the expression of tight junction ZO-1 and occludin in colon tissue were upregulated, and claudin-2 was downregulated. Ultimately, the serum content of tumor necrosis (TNF)-α, interleukin (IL)-1ß, and IL-6 was decreased. Moreover, the combined BBR with PT significantly promoted the restoration of gut microbiota. The relative abundance of Firmicutes and Lactobacillus was significantly increased by the supplement of PT and DHP, and the relative abundance of Proteobacteria was downregulated. CONCLUSIONS: Our study may provide a new perspective that the selection of pharmaceutical excipients could be a crucial factor affecting the drugs' therapeutic efficiency outcome.

VISTA inhibitors in cancer immunotherapy: a short perspective on recent progresses.

V-domain immunoglobulin (Ig) suppressor of T cell activation (VISTA) is a novel negative checkpoint regulator that mediates T cell proliferation and cytokine production. The VISTA signaling pathway blockade has been proved as a promising strategy for cancer immunotherapy. Recent VISTA sequence analysis and crystal structure investigations have revealed its independent and unique function as compared with B7 family members, such as PD-1. This review will discuss VISTA binding partners and compare the structural differences between VISTA and other B7 family members, focusing on VISTA functions in immune activation and maintaining T cell quiescence. Recent progress and the therapeutic potential of biomacromolecules, such as monoclonal antibodies (mAbs) and small molecules targeting VISTA, are also discussed. Among these, a first-in-class small-molecule antagonist, CA-170, is highlighted.

Management of the Cavity After Removal of Giant Cell Tumor of the Bone.

Purpose: To find out the most appropriate management scheme through the analysis and comparison of different inactivation methods and filling materials. Method: A systematic literature search was performed using the terms, anhydrous ethanol, phenol, hypertonic saline, cryotherapy, thermal therapy, bone reconstruction, GCTB, and etc., Selected articles were studied and summarized. The mechanism, clinical effects, and influence on bone repair of various methods are presented. Recent developments and perspectives are also demonstrated. Recent Findings: Compared to curettage alone, management of the residual cavity can effectively reduce the recurrence of giant cell tumours of bone. It is a complex and multidisciplinary process that includes three steps: local control, cavity filling, and osteogenic induction. In terms of local control, High-speed burring can enlarge the area of curettage but may cause the spread and planting of tumour tissues. Among the inactivation methods, Anhydrous ethanol, and hyperthermia therapy are relatively safe and efficient. The combination of the two may achieve a better inactivation effect. When inactivating the cavity, we need to adjust the approach according to the invasion of the tumour. Filling materials and bone repair should also be considered in management.

MicroRNA­424 serves an anti­oncogenic role by targeting cyclin­dependent kinase 1 in breast cancer cells.

The aim of the present study was to define the function of microRNA­424­5p (miR­424) in breast cancer cells. The present study investigated the level and the potential function of miR­424 in breast cancer by reverse transcription­quantitative polymerase chain reaction assays. miR­424 expression was decreased in the majority of human breast cancer specimens and cell lines used in the present study. The MTT assay, plate colony formation assay and flow cytometry analyses were used to characterize the function of miR­424 in two types of breast cancer cell lines. Upregulation of miR­424 inhibited cellular proliferation and regulated the cell cycle by arresting cells in the G2/M cell phase. The dual­luciferase reporter assay was used to confirm the direct association between miR­424 and cyclin­dependent kinase 1 (CDK1). Silencing of CDK1 expression by CDK1 short interfering RNA also significantly suppressed cell proliferation and arrested cells in the G2/M cell phase. The results of the present study indicated that miR­424 can suppress cell proliferation and arrest cells in G2/M cell phase by negatively regulating CDK1 mRNA in human breast cancer, possibly through the Hippo pathway and the extracellular signal­regulated kinase pathway. The results of the present study provided novel evidence for the role of miR­424 in breast cancer.

A Mechanochromic and Photochromic Dual-Responsive Co-assembly with Multicolored Switch: A Peptide-Based Dendron Strategy.

In this contribution, we report a unique co-assembly composed of pyrene and spiropyran that were linked separately at the focal point of the same peptide-based dendron (Phe-Glu), in which the dendrons offer driving forces for the coaggregation. A series of co-assemblies with different weight ratios (Py-Phe-Glu/SP-Phe-Glu) were prepared and the morphology could be tuned. It is found that the resulting stable co-assembled organogel is double switchable triggered by light and heat. TEM revealed that, in the xerogel, Py-Phe-Glu formed rigid rod nanofibers with large diameters and acted as a rigid sketelon where the gracile interwoven fibrous structure of SP-Phe-Glu grew. More interestingly, the original powder of the co-assembled xerogel (1.0 mg/0.1 mg) not only displayed a sequential high-contrast tricolored switch from dark blue to bright cyan and to red under external force but also presented multistate accessible photochromic properties. Such mechanochromic and photochromic behaviors of the xerogel are mainly due to the transition of different excimers of pyrene and the force/photoinduced ring-opening reaction of spiropyran. It is rarely reported that self-assembled soft materials achieve mechanochromic and photochromic dual-responsive behaviors with a high-contrast multicolored switch. We believe the co-assembly strategy based on polypeptide dendrons can be extended to other systems for establishing novel intelligent fluorescent materials.

Silencing of ASPP2 promotes the proliferation, migration and invasion of triple-negative breast cancer cells via the PI3K/AKT pathway.

Apoptosis-stimulating p53 protein 2 (ASPP2) is an apoptosis inducer that acts via binding with p53 and then enhancing the transcriptional activities toward pro­apoptosis genes. ASPP2 has recently been reported to serve a major role in p53­independent pathways. Triple­negative breast cancer (TNBC) is a type of breast cancer that is more aggressive and highly lethal when p53 is mutated. In the present study, the mRNA level of ASPP2 was found to be suppressed in breast tumors compared with that in adjacent normal breast tissues, and the expression of ASPP2 was also decreased in a series of breast cancer cell lines compared with that in MCF­10A normal breast cells. Downregulation of ASPP2 by specific small interfering RNA (siRNA) transfection was able to promote cell growth, reduce cell apoptosis, and contribute to cell migration and invasion. Furthermore, downregulation of ASPP2 promoted cell epithelial­mesenchymal transition (EMT) in MDA­MB­231 and HCC­1937 TNBC cells. Furthermore, it was found that when ASPP2 siRNA was transfected into MDA­MB­231 and HCC­1937 cells, the expression of phosphoinositide­3­kinase regulatory subunit 1 (p85α) decreased and phosphorylation of protein kinase B (AKT) increased, which are key molecular regulators in the phosphatidylinositol 3-kinase (PI3K)/AKT pathway. In conclusion, the present data indicated that ASPP2 had a crucial influence on the proliferation and metastasis in TNBC, and that the functional mechanism may be p53­independent to a great extent. ASPP2 and its link with the PI3K/AKT pathway deserve further investigation and may provide novel insights into therapeutic targets for TNBC.

The microRNAs miR-200b-3p and miR-429-5p target the LIMK1/CFL1 pathway to inhibit growth and motility of breast cancer cells.

Triple-negative breast cancer (TNBC) has the worst prognosis of all subtypes of breast cancer (BC), with limited options for conventional therapy and no targeted therapies. MicroRNAs (miRNAs) are small noncoding RNAs that negatively regulate gene expression. In this study, we aimed to determine whether two members of the miR-200 family, miR-200b-3p and miR-429-5p, are involved in BC cell proliferation and motility and to elucidate their target genes and pathways. We performed a meta-analysis that reveals down-regulated expression of miR-200b-3p and miR-429-5p in BC tissues and cell lines, consistent with a lower expression of miR-200b-3p and miR-429-5p in MDA-MB-231 and HCC1937 cells than in MCF-7 and MCF-10 cells. Overexpression of miR-200b-3p and miR-429-5p significantly inhibited the proliferation, migration, and invasion of TNBC cells; suppressed the expression of markers for proliferation and metastasis in TNBC cells. We next demonstrated that LIM domain kinase 1 (LIMK1) is a direct target gene of miR-200b-3p and miR-429-5p. Inhibition of LIMK1 reduced the expression and phosphorylation of cofilin 1 (CFL1), which polymerizes and depolymerizes F-actin and G-actin to reorganize cellular actin cytoskeleton. In addition, transfection with mimics for miR-200b-3p and miR-429-5p arrested G2/M and G0/G1 cell cycles respectively, suppressed the expression of the cell cycle-related complexes, cyclin D1/CDK4/CDK6 and cyclin E1/CDK2, in TNBC cells. In conclusion, miR-200b-3p and miR-429-5p suppress proliferation, migration, and invasion in TNBC cells, via the LIMK1/CFL1 pathway. These results provide insight into how specific miRNAs regulate TNBC progression and suggest that the LIMK1/CFL1 pathway is a therapeutic target for treating TNBC.

MicroRNA-340 inhibits invasion and metastasis by downregulating ROCK1 in breast cancer cells.

MicroRNAs (miRNAs/miRs) are 19-25 nucleotide-long, non-coding RNAs that regulate the expression of target genes at the post-transcriptional level. In the present study, the role of miR-340 in breast cancer (BC) was investigated. The overexpression of miR-340 significantly inhibited the proliferation, migration and invasion of human breast MDA-MB-231 cancer cells in vitro. The Rho-associated, coiled-coil containing protein kinase 1 (ROCK1) gene was identified as a target of miR-340; its expression was downregulated by overexpression of miR-340 by binding to its 3'-untranslated region. The short interfering RNA-mediated silencing of ROCK1 was also performed, which phenocopied the effects of miR-340 overexpression. An inhibitor of miR-340 was used to suppress miR-340 expression, which led to increased expression of ROCK1, thus improving the proliferation, migration and invasion of MDA-MB-231 cells. Data from the present study suggest that miR-340 inhibits MDA-MB-231 cell growth and its downregulation may lead to the progression and metastasis of BC. Thus, miR340 may act as a tumor-suppressor agent that could serve a key role in the diagnosis and therapy of BC.

Inhibition of RAB1A suppresses epithelial-mesenchymal transition and proliferation of triple-negative breast cancer cells.

RAB1A acts as an oncogene in various cancers, and emerging evidence has verified that RAB1A is an mTORC1 activator in hepatocellular and colorectal cancer, but the role of RAB1A in breast cancer remains unclear. In this investigation, RAB1A siRNA was successfully transfected in MDA-MB-231 and BT-549 human triple-negative breast cancer cells, and verified by real­time quantitative polymerase chain reaction and western blotting. Then, MTT cell proliferation, colony formation, cell invasion and wound healing assays were performed to characterize the function of RAB1A in the breast cancer cell lines. Downregulation of RAB1A inhibited cellular growth, cell migration, cell invasion and cell epithelial-mesenchymal transition. Furthermore, compared with NC siRNA transfected cells, RAB1A siRNA transfected breast cancer cells inhibited the phosphorylation of S6K1, the effector molecular of mTORC1. Collectively, our data suggested that RAB1A acts as an oncogene by regulating cellular proliferation, growth, invasion and metastasis via activation of mTORC1 pathway in triple-negative breast cancer.

MicroRNA-7 inhibits proliferation, migration and invasion of thyroid papillary cancer cells via targeting CKS2.

The purpose of this study was to examine the expression levels of microRNA-7 (miR-7) in human thyroid papillary cancer and its potential role in disease pathogenesis. The expression levels of different miRNAs were detected by miRNA-microarray analysis in ten thyroid papillary cancer specimens and adjacent normal thyroid cancer tissues. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was conducted to determine the expression level of miR-7 in both thyroid papillary cancer tissues and cell lines. To characterize the function of miR-7, MTT assay, colony formation assay, cell migration assay, cell invasion assay, cell cycle assay and cell apoptosis assay were used. Luciferase reporter assays were performed to validate the regulation of a putative target of miR-7, in corroboration with western blot assays. Finally, MTT assay, cell migration assay, cell invasion assay and cell cycle assay were used to indicate the roles of endogenous cyclin-dependent kinase regulatory subunit 2 (CKS2) in thyroid papillary cancer cells. Our results reveal that miR-7 expression was relatively decreased in thyroid papillary cancer specimens and cell lines compared with adjacent normal tissues and normal thyroid cells. Overexpression of miR-7 inhibited cellular proliferation, suppressed cellular migration and invasion, caused a G0/G1 arrest in vitro. Dual-luciferase reporter assays showed that miR-7 binds the 3'-untranslated region (3'-UTR) of CKS2. Western blotting showed that miR-7 negatively regulated CKS2 protein expression. As its downstream genes, cyclin B1 (G2/mitotic-specific cyclin-B1) and cdk1 (cyclin-dependent kinase 1) were regulated by miR-7 and CKS2 axis. Knockdown of CKS2 expression by CKS2-siRNA in TPC1 and K1 cells also significantly suppressed cell proliferation, cell migration and invasion. Our results demonstrated for the first time that miR-7 functions as a tumor suppressor and plays an important role in inhibiting the tumorigenesis through targeting CKS2 in thyroid papillary cancer cells.