Interference of lysine-specific demethylase 1 inhibits cellular invasion and proliferation in vivo in gastric cancer MKN-28 cells

BackgroundLysine-specific demethylase 1(LSD1), the first identified histone demethylase, plays an important role in the epigenetic regulation of gene activation and repression. Up-regulated LSD1expression has been reported in several malignant tumors.Our aim, therefore, was to better understand the mechanisms underlying the upregulation of LSD1 in gastric cancer.MethodsWe used lentiviral shRNA to knockdown LSD1 in the gastric cancer MKN-28 cell line. Cell proliferation was measured by MTT assay while cell apoptosis was assessed by Annexin V-FITC/PI double staining flow cytometry. The invasive potential of gastric cancer cells was determined by matrigel invasion assay. Protein expression was detected by Western blot. In vivo, the effect of knocking down LSD1 on tumor growth and protein expression in gastric cancer cells in nude mice was investigated.ResultsLSD1 knockdown in MKN-28 cell lines resulted in increasing the activity of cisplatin in vitro and the inhibition of cancer cell proliferation and invasion, and induced cell apoptosis. The expression of TGF-β1, VEGF, Bcl-2, β-catenin, p-ERK and p-Smad 2/3 proteins was inhibited in LSD1 knockdown cells. Moreover, in an in vivo model of gastric cancer, LSD1 knockdown suppressed tumor growth and protein expression.ConclusionLSD1 knockdown affected the fuction of gastric cancer MKN-28 cell line. LSD1 may be a latent target in the diagnosis and therapy of gastric cancer.     

Hesperetin inhibits Eca-109 cell proliferation and invasion by suppressing the PI3K/AKT signaling pathway and synergistically enhances the anti-tumor effect of 5-fluorouracil on esophageal cancer in vitro and in vivo

Previously, we reported that hesperetin exhibited pro-apoptotic activity against esophageal cancer in vitro and in vivo. Here, we examined whether hesperetin inhibits cell proliferation and invasion and synergistically enhances the anti-tumor effect of 5-fluorouracil (5-FU) in esophageal cancer. Flow cytometry, EdU staining, and transwell invasion assays using Eca-109 cells showed that hesperetin induced cell cycle arrest at the G0/G1 phase and inhibited cell proliferation and invasion significantly. Moreover, hesperetin suppressed the expression of phosphorylated PI3K/AKT, cyclin D1, MMP-2, and MMP-9 and increased phosphorylated PTEN and p21 in Eca-109 cells. Hesperetin combined with 5-FU inhibited cell growth more effectively than did either drug alone in Eca-109 cells and in a xenograft mouse model. Hoechst 33258, Annexin V-PE/7-ADD double staining and TUNEL assay showed more apoptotic cells in the combination treatment group than in either individual treatment group. The combination down-regulated protein levels of Bcl-2 and up-regulated those of Bax, cleaved caspase-3, and cleaved caspase-9 more effectively than did either drug alone. These data suggest that hesperetin inhibited esophageal cancer cell proliferation and invasion by suppressing the PI3K/AKT signaling pathway. In conclusion, 5-FU and hesperetin exerted synergistic antitumor effects in vivo and in vitro and could constitute a novel therapeutic approach for esophageal cancer.

Effects of hesperetin on the proliferation and invasion of esophageal cancer cells and its synergistic anti-cancer effect with 5-FU.     

Carfilzomib interacts synergistically with histone deacetylase inhibitors in mantle cell lymphoma cells in vitro and in vivo

Interactions between the proteasome inhibitor carfilzomib and the histone deacetylase (HDAC) inhibitors vorinostat and SNDX-275 were examined in mantle cell lymphoma (MCL) cells in vitro and in vivo. Coadministration of very low, marginally toxic carfilzomib concentrations (e.g., 3-4 nmol/L) with minimally lethal vorinostat or SNDX-275 concentrations induced sharp increases in mitochondrial injury and apoptosis in multiple MCL cell lines and primary MCL cells. Enhanced lethality was associated with c-jun-NH,-kinase (JNK) 1/2 activation, increased DNA damage (induction of λH2A.X), and ERK1/2 and AKT1/2 inactivation. Coadministration of carfilzomib and histone deacetylase inhibitors (HDACI) induced a marked increase in reactive oxygen species (ROS) generation and G(2)-M arrest. Significantly, the free radical scavenger tetrakis(4-benzoic acid) porphyrin (TBAP) blocked carfilzomib/HDACI-mediated ROS generation, λH2A.X formation, JNK1/2 activation, and lethality. Genetic (short hairpin RNA) knockdown of JNK1/2 significantly attenuated carfilzomib/HDACI-induced apoptosis, but did not prevent ROS generation or DNA damage. Carfilzomib/HDACI regimens were also active against bortezomib-resistant MCL cells. Finally, carfilzomib/vorinostat coadministration resulted in a pronounced reduction in tumor growth compared with single agent treatment in an MCL xenograft model associated with enhanced apoptosis, λH2A.X formation, and JNK activation. Collectively, these findings suggest that carfilzomib/HDACI regimens warrant attention in MCL.     

Methyltransferase G9A regulates T cell differentiation during murine intestinal inflammation

Inflammatory bowel disease (IBD) pathogenesis is associated with dysregulated CD4⁺ Th cell responses, with intestinal homeostasis depending on the balance between IL-17–producing Th17 and Foxp3⁺ Tregs. Differentiation of naive T cells into Th17 and Treg subsets is associated with specific gene expression profiles; however, the contribution of epigenetic mechanisms to controlling Th17 and Treg differentiation remains unclear. Using a murine T cell transfer model of colitis, we found that T cell–intrinsic expression of the histone lysine methyltransferase G9A was required for development of pathogenic T cells and intestinal inflammation. G9A-mediated dimethylation of histone H3 lysine 9 (H3K9me2) restricted Th17 and Treg differentiation in vitro and in vivo. H3K9me2 was found at high levels in naive Th cells and was lost following Th cell activation. Loss of G9A in naive T cells was associated with increased chromatin accessibility and heightened sensitivity to TGF-β1. Pharmacological inhibition of G9A methyltransferase activity in WT T cells promoted Th17 and Treg differentiation. Our data indicate that G9A-dependent H3K9me2 is a homeostatic epigenetic checkpoint that regulates Th17 and Treg responses by limiting chromatin accessibility and TGF-β1 responsiveness, suggesting G9A as a therapeutic target for treating intestinal inflammation.     

Aminopeptidase N inhibitor 4cc synergizes antitumor effects of 5-fluorouracil on human liver cancer cells through ROS-dependent CD13 inhibition

Aminopeptidase N (APN, also known as CD13) is involved in cellular processes of various types of tumors and a potential anti-cancer therapeutic target. Here, we report the effect of an APN inhibitor 4cc in enhancing sensitivity of hepatocellular carcinoma (HCC) cell lines and xenograft model in response to 5-fluorouracil (5-FU) in vivo and in vitro. The treatment of the combination of 4cc with 5-FU, compared to the combination of bestain with 5-FU, markedly suppressed cell growth and induced apoptosis of HCC cells, accompanying the increase in the level of reactive oxygen species (ROS) and followed by a decrease in the mitochondrial membrane potential (ΔΨM). Furthermore, the combination of 4cc and 5-FU showed a significant inhibitory effect on the growth of HCC xenograft tumors. In addition, following the treatment of 4cc, APN activity and clonogenic formation and the number of CD13-positive cells in PLC/PRF/5 cells were significantly decreased, suggesting that 4cc may also inhibit liver cancer stem cells by CD13 inhibition. These results showed that the APN inhibitor 4cc synergizes antitumor effects of 5-FU on human liver cancer cells via ROS-mediated drug resistance inhibition and concurrent activation of the mitochondrial pathways of apoptosis.     

Circular RNA SMARCA5 inhibits gastric cancer progression through targeting the miR-346/ FBXL2 axis

Circular RNA (circRNA) SMARCA5 (circSMARCA5) is a cancer-related circRNA that has been observed to be involved in the progression of several types of cancer. However, the role of circSMARCA5 in gastric cancer has not been reported. In the present study, we aimed to explore the function and mechanism of circSMARCA5 in gastric cancer. Our results showed that circSMARCA5 expression was significantly decreased in human gastric cancer tissues and cell lines. Further in vitro investigations demonstrated that overexpression of circSMARCA5 in SGC7901 cells inhibited cell proliferation, migration and invasion. Luciferase reporter assays proved that circSMARCA5 acted as a sponge for miroRNA-346 (miR-346) and regulated the expression of F-Box and leucine rich repeat protein 2 (FBXL2). Furthermore, transfection of miR-346 mimics into cells overexpressing circSMARCA5 blocked the function of circSMARCA5. Finally, we found that knockdown FBXL2 significantly reversed the effects of miR-346 inhibitor on gastric cell proliferation, migration and invasion. Collectively, circSMARCA5 exhibited a tumor suppressor-like activity in gastric cancer via regulating the miR-346/FBXL2 axis.

Circular RNA (circRNA) SMARCA5 (circSMARCA5) is a cancer-related circRNA that has been observed to be involved in the progression of several types of cancer.     

Preparation and in vitro evaluation of 5-flourouracil loaded magnetite–zeolite nanocomposite (5-FU-MZNC) for cancer drug delivery applications

In this work, super paramagnetic magnetite nanoparticles were synthesized onto/into zeolite, then loaded with anti-cancer drug 5-fluorouracil (5-FU). The physical properties of the prepared nanocomposite and drug loaded nanocomposite were characterized using different techniques. The drug loading and releasing behavior of the magnetic nanocarrier was investigated and the drug-loaded nanoparticles exhibited a sustained release of drug without any burst release phenomenon. Furthermore, 5-FU loaded MZNC were evaluated for its biological characteristics. The functional 5-FU-MZNC has been triggered intra-cellular release of the cancer therapeutic agent 5-fluorouracil (5-FU). Cytotoxic effects of 5-FU loaded MZNC on human gastric carcinoma (AGS) cells were determined by real time cell analysis and colorimetric WST-1 cell viability assay. Apoptosis of cells was further investigated by Annexin-V staining which indicates the loss of cell membrane integrity. According to our results, 5-FU-MZNC showed a concentration-dependent cell proliferation inhibitory function against AGS cells. Morphologic and apoptotic images were consistent with the cytotoxicity results. In conclusion, 5-FU loaded MZNC efficiently inhibit the proliferation of AGS cells in vitro through apoptotic mechanisms, and may be a beneficial agent against cancer, however further animal study is still required.     

The novel anthraquinone derivative IMP1338 induces death of human cancer cells by p53-independent S and G2/M cell cycle arrest

To identify novel small molecules that induce selective cancer cell death, we screened a chemical library containing 1040 compounds in HT29 colon cancer and CCD18-Co normal colon cells, using a phenotypic cell-based viability assay system with the Cell Counting Kit-8 (CCK-8). We discovered a novel anthraquinone derivative, N-(4-[{(9,10-dioxo-9,10-dihydro-1-anthracenyl)sulfonyl}amino]phenyl)-N-methylacetamide (IMP1338), which was cytotoxic against the human colon cancer cells tested. The MTT cell viability assay showed that treatment with IMP1338 selectively inhibited HCT116, HCT116 p53^−/−, HT29, and A549 cancer cell proliferation compared to that of Beas2B normal epithelial cells. To elucidate the cellular mechanism underlying the cytotoxicity of IMP1338, we examined the effect of IMP1338 on the cell cycle distribution and death of cancer cells. IMP1338 treatment significantly arrested the cell cycle at S and G2/M phases by DNA damage and led to apoptotic cell death, which was determined using FACS analysis with Annexin V/PI double staining. Furthermore, IMP1338 increased caspase-3 cleavage in wild-type p53, p53 knockout HCT116, and HT29 cells as determined using immunoblotting. In addition, IMP1338 markedly induced the phosphorylation of histone H2AX and Chk1 in both cell lines while the combination of 5-fluorouracil (5-FU) and radiation inhibited the viability of HCT116, HCT116 p53^−/−, and HT29 cells compared to 5-FU or radiation alone. Our findings indicated that IMP1338 induced p53-independent cell death through S and G2/M phase arrest as well as DNA damage. These results provide a basis for future investigations assessing the promising anticancer properties of IMP1338.     

Low-dose all-trans retinoic acid enhances cytotoxicity of cisplatin and 5-fluorouracil on CD44+ cancer stem cells

Cis-diamminedichloridoplatinum(II)(CDDP)-based combination chemotherapy is frequently used in gastrointestinal cancer. The synergistic mechanism of all-trans retinoic acid (ATRA), cisplatin (CDDP) and 5-fluorouracil (5-FU) in combination remains unclear. Despite their potent antitumor properties, resistance to CDDP and 5-FU develops frequently in tumors. To clarify this mechanism, we determined the sensitivity to each drug and their combination in two gastrointestinal cancer stem cells (CSCs) subpopulation.Here, we report the identification and separation of CD44⁺ cells from human gastric carcinoma (AGS) and human esophageal squamous cell carcinoma (KYSE-30) cancer cell lines by magnetic activated cell sorting (MACS). We allowed the CD44^± cells to grow 6 days at a subtoxic concentration of ATRA and then treated with different concentration of CDDP and 5-FU for 24 h. The cytotoxicity was examined by cell proliferation MTT assay. Additionally, AO/EB staining was used for detection of apoptotic cells. In order to determine whether the growth inhibition was also associated with changes in cell cycle distribution, cell cycle analysis was performed using flow cytometry.Low concentration of ATRA (1 μM, 6days) followed by 5-FU and CDDP was found to be more effective than either drugs alone, thus resulting in synergistic cytotoxicity in Kyse-30 and AGSCD44^± cells. Furthermore, there was an indication that the combination of ATRA with 5FU and CDDP caused an increase in cell cycle arrest in G2/M and G0/G1.We conclude that low concentration of ATRA enhances the cytotoxicity of CDDP and 5FU by facilitating apoptosis and cell cycle arrest in gastrointestinal CSCs and provide a rational basis for the design of novel, well-tolerated CDDP- and 5FU-based chemotherapy in human gastrointestinal carcinoma.     

Gene expression profile of 5-fluorouracil metabolic enzymes in laryngeal cancer cell line: Predictive parameters for response to 5-fluorouracil-based chemotherapy

Background

5-fluorouracil (5-FU) is an antifolate chemotherapeutic that has become established in many therapeutic regimes, but sensitivity variations and development of resistance are common problems that limit the efficiency of the treatments. Inter-individual variations to 5-FU outcome have been attributed to different expression profiles of genes related to folate metabolism.

Methods

To elucidate the mechanisms of variations to 5-FU outcome, the authors investigated MTHFR, DHFR, TYMS and SLC19A1 folate genes expression for 5-FU response in laryngeal cancer cell line (Hep-2). Concentrations of 10, 50, and 100 ng/mL of 5-FU chemotherapeutic were added separately in Hep-2 cell line for 24 hours at 37 °C. Cell sensibility was evaluated with fluorescein isothiocyanate (FITC) label Bcl-2 by flow cytometry. The real-time quantitative PCR (qPCR) technique was performed for quanti?cation of gene expression using TaqMan^® Gene Expression Assay. ANOVA and Bonferroni's post hoc tests were utilized to statistical analysis.

Results

The numbers of viable Hep-2 cells with 10, 50, and 100 ng/mL concentrations of 5-FU chemotherapy were 15.87, 28.3 and 68.9%, respectively. Statistical analysis showed significant association between control group and increased expression for TYMS gene in cells treated with 100 ng/mL/5-FU chemotherapy (P < 0.05).

Conclusions

The authors found association between the highest 5-FU dose chemotherapy and increased expression levels for TYMS folate gene in laryngeal cancer cell line. Although these experiments were performed in vitro, the results suggest that genetic factors are thought to play an important role in drug metabolism and may be useful for predicting treatment outcomes.     

Expression of livin in gastric cancer and induction of apoptosis in SGC-7901 cells by shRNA-mediated silencing of livin gene

Background

Because of increased resistance to apoptosis in tumor cells, inhibition of specific anti-apoptotic factors may provide a rational approach for the development of novel therapeutic strategies. Livin, a novel inhibitor of apoptosis protein family, has been found to be expressed in various malignancies and is suggested to have poorly prognostic significance. However, no data are available concerning the significance of livin in gastric cancer. In this study, we detected the expression of livin in human gastric carcinoma and investigated the apoptotic susceptibility of SGC – 7901 cell by shRNA-mediated silencing of the livin gene.

Methods

The mRNA and protein expression of livin were analyzed by RT-PCR and western blot assay. The relationship between livin expression and clinical pathologic parameters was investigated. The small interfering RNA eukaryotic expression vector specific to livin was constructed by gene recombination, and the nucleic acid was sequenced. Then it was transfected into SGC-7901 cells by Lipofectamin 2000. RT-PCR and Western blot assay were used to validate gene-silencing efficiency of livin in SGC-7901 cells. Stable clones were obtained by G418 screening. The cell apoptosis was assessed by flow cytometry (FCM). Cell growth state and 50 % inhibition concentration (IC50) of 5-FU and cisplatin was determined by MTT method.

Results

The expression of livin mRNA and protein were detected in 19 of 40 gastric carcinoma cases (47.5%) and SGC-7901 cells. No expression of livin was detected in tumor adjacent tissues and benign gastric lesion. The positive correlation was found between livin expression and poor differentiation of tumors as well as lymph node metastases (P < 0.05). Four small interfering RNA eukaryotic expression vector specific to livin were constructed by gene recombination. And one of them can efficiently decrease the expression of livin, the inhibition of the gene was not less than 70% (P < 0.01). The recombinated plasmids were extracted and transfected gastric cancer cells. The stable clones were obtained by G418 screening, and were amplified and cultured. When livin gene was silenced, the reproductive activity of the gastric cancer cells was significantly lower than the control groups(P < 0.05). The study also showed that IC50 of 5-Fu and cisplatin on gastric cancer cells treated by shRNA was decreased and the cells were more susceptible to proapoptotic stimuli (5-Fu and cisplatin) (P < 0.01).

Conclusions

Livin is overexpressed in gastric carcinoma with a relationship to tumor differentiation and lymph node metastases, which is suggested to be one of the molecular prognostic factors for some cases of gastric cancer. ShRNA can inhibit livin expression in SGC-7901 cells and induce cell apoptosis. Livin may serve as a new target for apoptosis-inducing therapy of gastric cancer.     

胃癌间充质干细胞高表达G6PD促进肿瘤细胞迁移

摘要：目的?探究胃癌间充质干细胞(gastric cancer mesenchymal stem cells, GCMSCs)葡萄糖-6-磷酸脱氢酶(G6PD)的表达及其在肿瘤细胞迁移中的作用。方法?采用western blot检测G6PD在GCMSCs、骨髓间充质干细胞(bone marrow mesenchymal stem cells, BMMSCs)和胃癌细胞来源外泌体(exosome)预处理BMMSCs中的表达水平。生化分析仪检测MSCs 中G6PD的活性。活性氧(ROS)探针检测MSCs中ROS的表达水平。台盼蓝染色法检测细胞存活率。细胞迁移试验检测G6PD对MSCs和胃癌细胞迁移的影响。使用CCK-8试剂盒检测MSCs增殖能力。结果?GCMSCs 中G6PD的表达量及活性较BMMSCs明显升高(t分别为7.497、11.75，P<0.01)，且GCMSCs促进胃癌细胞迁移能力较BMMSCs明显增强(P<0.05)。胃癌细胞来源的exosome通过调节P53，上调BMMSCs 中G6PD的表达水平(P<0.01)。G6PD可清除MSCs细胞内活性氧，维持MSCs在低胎牛血清(t=11.29，P<0.01)或H2O2?(t=3.444，P<0.05)的条件下存活，并促进MSCs增殖和迁移(P<0.01)。胃癌患者肿瘤基质细胞G6PD的表达与胃癌组织大小及转移有关(P<0.05)。结论?GCMSCs通过高表达G6PD促进胃癌细胞迁移。肿瘤基质G6PD有望成为肿瘤诊断和预后监测的潜在标志物。     

Notoamide-type alkaloid induced apoptosis and autophagy via a P38/JNK signaling pathway in hepatocellular carcinoma cells

Bioassay-guided fractionation of a coral-associated fungus Aspergillus ochraceus LZDX-32-15 resulted in the isolation of eleven notoamide-type alkaloids, including four new congeners, namely notoamides W-Z (1–4). The structures of the new alkaloids were determined by extensive analyses of spectroscopic data (1D and 2D NMR, HRESIMS), while ECD data were used for the configurational assignment. Three alkaloids (6, 10, 11) exerted potent inhibition against a panel of hepatocellular carcinoma (HCC) cell lines with IC₅₀ values ranging from 0.42 to 3.39 μM, that are comparable to the data for paclitaxel. Notoamide G (6) inhibited the viability of HepG2 and Huh-7 cells via both apoptosis and autophagy pathways. Notoamide G activated the expression of caspase-3, caspase-8, and caspase-9, in association with the degradation of the downstream gene PARP in a dose-dependent manner, suggesting that notoamide G induced apoptosis via a mitochondrial pathway and a dead receptor-mediated pathway. In addition, notoamide G increased the autophagic vacuole in both HepG2 and Huh-7 cells in a dose-dependent manner after 24 h through the significant upregulation of the key proteins Beclin1 and LC3B. Further investigation revealed that notoamide G promoted P38 and JNK phosphorylation, whereas the total protein of P-38 and JNK was slightly influenced. Accordingly, the antitumor proliferation of notoamide G in HCC cells was mechanistically mediated by apoptosis and autophagy through a P38/JNK signaling pathway, while notoamide G was considered as a potent lead for further development as an antitumor agent.

Eleven notoamides including four new congeners were isolated from Aspergillus ochraceus. Notoamide G inhibited the viability of hepatocellular carcinoma cell lines by regulation of apoptosis and autophagy through P38/JNK signaling pathway.     

Tannic acid-stabilized gold nano-particles are superior to native tannic acid in inducing ROS-dependent mitochondrial apoptosis in colorectal carcinoma cells via the p53/AKT axis

Gold nanoparticle formulated tannic acid (AuNP-TA) was synthesized, and its anticancer activity was compared to that of free tannic acid (TA). The half maximal inhibitory concentration (IC₅₀) was reduced by half when cell lines were treated with AuNP-TA as compared to IC₅₀ values upon free TA treatment. Both showed better cytotoxic activity in HCT116 cell line as compared to MCF7 and HepG2. AuNP-TA induced death of HCT116 cells was associated with characteristic apoptotic changes. At the same treatment dose, AuNP-TA generated more ROS, caused a more extensive DNA damage and promoted higher expression of p53 and p21 than TA. Treatment with AuNP-TA regulated generation of p53 and ROS bi-directionally. Binding studies showed that TA lowered the expression of Akt, which inhibited the survival of colon cancer cells. Also, cell cycle arrest at the G2/M phase, enhanced expression of caspase-3/9, Bak, and Bax, loss of mitochondrial membrane potential, and enhanced level of cytosolic cytochrome c were observed in AuNP-TA treated HCT116 cells. Thus, AuNP-TA is more efficient than TA in inducing apoptotic cell death of HCT116 cells via the ROS/P53/Akt axis.

Tannic acid and AuNP-TA lead to death of colon cancer cells via the ROS/p53/Akt pathway, and AuNP-TA is more potent.     

Tamoxifen reduces P-gp-mediated multidrug resistance via inhibiting the PI3K/Akt signaling pathway in ER-negative human gastric cancer cells

Multidrug resistance (MDR), mediated by overexpression of drug efflux transporters such as P-glycoprotein (P-gp), is a major problem limiting successful chemotherapy of gastric cancer. Tamoxifen (TAM), a triphenylethylene nonsteroidal antiestrogen agent, shows broad-spectrum antitumor properties. Emerging studies demonstrated that TAM could significantly reduce the MDR in a variety of human cancers. Here we investigated the effects and possible underlying mechanisms of action of TAM on the reversion of MDR in ER-negative human gastric cancer cells. Our results demonstrated that in MDR phenotype SGC7901/CDDP gastric cancer cells TAM dramatically lowered the IC₅₀ of CDDP, 5-FU and ADM, increased the intracellular Rhodamine123 accumulation and induced G0/G1 phase arrest, while G2/M phase decreased accordingly. Furthermore, at the molecular level, TAM substantially decreased the expression of P-gp, p-Akt and the Akt-regulated downstream effectors such as p-GSK-3β, p-BAD, Bcl-XL and cyclinD1 proteins without affecting the expression of t-Akt, t-GSK-3β, t-BAD proteins in SGC7901/CDDP cells. Thus, our findings demonstrate that TAM reverses P-gp-mediated gastric cancer cell MDR via inhibiting the PI3K/Akt signaling pathway.     

miR-935 promotes gastric cancer cell proliferation by targeting SOX7

Gastric cancer is the most common cancer in the world, miRNAs have been demonstrated to play critical role in the development and progression of gastric cancer, such as miR-7, miR-217 and miR-335. Here, we found miR-935 was upregulated in gastric cancer tissues and cells. Overexpression of miR-935 promoted cell proliferation and tumorigenesis in vitro determined by MTT analysis, colony formation analysis, BrdU cell proliferation analysis and soft agar growth analysis, knockdown of miR-935 reduced these effects. Tumor suppressor sex-determining region Y-box 7 (SOX7) was the direct target of miR-935, overexpression of miR-935 inhibited SOX7 expression, but promoted the levels CCND1 and C-MYC which promotes cell proliferation and tumorigenesis, knockdown of miR-935 increased SOX7 level, and inhibited CCND1 and C-MYC expression. Synchronous knockdown of miR-935 and SOX7 promoted cell proliferation and tumorigenesis in vitro, confirming miR-935 regulated gastric cancer cell proliferation by inhibiting SOX7. In summary, we found miR-935 contributed to cell proliferation of gastric cancer through targeting SOX7.