MIR143HG promotes methylation of transcription factor HOXB7 promoter by recruiting methyltransferase DNMT1 to prevent the progression of colon cancer.

In recent years, accumulating evidence has demonstrated the role of long noncoding RNAs (lncRNAs) in colon cancer. We aim to investigate the role of MIR143HG, also known as CARMN (Cardiac mesoderm enhancer-associated noncoding RNA) in colon cancer and explore the related mechanisms. An RNAseq data analysis was performed to screen differentially expressed lncRNAs associated with colon cancer. Next, MIR143HG expression was quantified in colon cancer cells. Moreover, the contributory roles of MIR143HG in the progression of colon cancer with the involvement of DNMT1 and HOXB7 (Homeobox B7) were evaluated after restored MIR143HG or depleted HOXB7. Finally, the effects of MIR143HG were investigated in vivo by measuring tumor formation in nude mice. High-throughput transcriptome sequencing was employed to validate the specific mechanisms by which MIR143HG and HOXB7 affect tumor growth in vivo. MIR143HG was found to be poorly expressed, while HOXB7 was highly expressed in colon cancer. MIR143HG could promote HOXB7 methylation by recruiting DNMT1 to reduce HOXB7 expression. Upregulation of MIR143HG or downregulation of HOXB7 inhibited cell proliferation, invasion and migration and facilitated apoptosis in colon cancer cells so as to delay the progression of colon cancer. The same trend was identified in vivo. Our study provides evidence that restoration of MIR143HG suppressed the progression of colon cancer via downregulation of HOXB7 through DNMT1-mediated HOXB7 promoter methylation. Thus, MIR143HG may be a potential candidate for the treatment of colon cancer.

LINC00858 promotes colon cancer progression through activation of STAT3/5 signaling by recruiting transcription factor RAD21 to upregulate PCNP.

The purpose of our investigation is to explore the putative molecular mechanisms underpinning LINC00858 involvement in colon cancer. The expression of LINC00858 in TCGA data was identified using the GEPIA website. Colon cancer cancerous tissues were clinically collected. The expression of LINC00858, RAD21, and PCNP in colon tissues or cells was determined using RT-qPCR. The interactions among LINC00858, RAD21, and PCNP promoter region were determined by means of RNA pull down, RIP, and ChIP assays. Cell proliferative, apoptotic, invasive, and migrated capabilities were evaluated. Western blot was conducted to determine RAD21, PCNP, phosphorylated (p)-STAT3, STAT3, p-STAT5 and STAT5 and apoptosis related proteins. A nude mouse model of colon cancer was constructed and tumorigenesis of colon cancer cells was observed. LINC00858 was upregulated in cancerous tissues and cells. LINC00858 recruited the transcription factor RAD21. Overexpression of LINC00858 promoted the binding of RAD21 and PCNP promoter region, which increased the expression of PCNP. Silencing of RAD21 or PCNP reversed the promoting effect of LINC00858 on the disease initiation and development. PCNP silencing inhibited proliferative ability and promoted apoptotic ability of cancerous cells via STAT3/5 inhibition, which was reversed by colivelin-activated STAT3. In vivo experiments further verified that LINC00858 enhanced the tumorigenicity of colon cancer cells in vivo by regulating the RAD21/PCNP/STAT3/5 axis. It indicated the promoting role of LINC00858 in colon cancer progression though activating PCNP-mediated STAT3/5 pathway by recruiting RAD21.

NR4A1 knockdown confers hepatoprotection against ischaemia-reperfusion injury by suppressing TGFß1 via inhibition of CYR61/NF-κB in mouse hepatocytes.

Nuclear receptor subfamily 4, group A, member 1 (NR4A1) can aggravate ischaemia-reperfusion (I/R) injury in the heart, kidney and brain. Thus, the present study aimed to unravel the role of NR4A1 on hepatic I/R injury. For this purpose, the mouse hepatic I/R model and H/R-exposed mouse hepatocytes model were established to stimulate the hepatic and hepatocellular damage. Then, the levels of ALT and AST as well as TNF-α and IL-1ß expression were measured in the mouse serum and supernatant of hepatocyte s, respectively. Thereafter, we quantified the levels of NR4A1, CYR61, NF-kB p65 and TGFß1 under pathological conditions, and their interactions were analysed using ChIP and dual-luciferase reporter gene assays. The in vivo and in vitro effects of NR4A1, CYR61, NF-kB p65 and TGFß1 on I/R-induced hepatic and H/R-induced hepatocellular damage were evaluated using gain- and loss-of-function approaches. NR4A1 was up-regulated in the hepatic tissues of I/R-operated mice and in H/R-treated hepatocytes. Silencing NR4A1 relieved the I/R-induced hepatic injury, as supported by suppression of ALT and AST as well as TNF-α and IL-1ß. Meanwhile, NR4A1 knockdown attenuated the H/R-induced hepatocellular damage by inhibiting the apoptosis of hepatocyte s. Moreover, we also found that NR4A1 up-regulated the expression of CYR61 which resulted in the activation of the NF-κB signalling pathway, thereby enhancing the transcription of TGFß1, which was validated to be the mechanism underlying the contributory role of NR4A1 in hepatic I/R injury. Taken together, NR4A1 silencing reduced the expression of CYR61/NF-κB/TGFß1, thereby relieving the hepatic I/R injury.

LncRNA SLCO4A1-AS1 modulates colon cancer stem cell properties by binding to miR-150-3p and positively regulating SLCO4A1.

Long non-coding RNAs (lncRNAs) play important roles in a range of different human cancers. However, the role of lncRNA solute carrier organic anion transporter family member 4A1-AS1 (SLCO4A1-AS1) in colon cancer remains enigmatic. Hence, we aimed to explore the specific role of SLCO4A1-AS1 in colon cancer stem cells. Colon cancer-related differentially expressed lncRNA and mRNA were screened using microarray-based analysis, and the expression of SLCO4A1-AS1 and SLCO4A1 in colon cancer tissues was determined using reverse transcription quantitative polymerase chain reaction and western blot analysis. The interaction among SLCO4A1-AS1, microRNA-150-3p (miR-150-3p) and SLCO4A1 was verified using dual-luciferase reporter assay, RNA immunoprecipitation and RNA pull-down. Moreover, SLCO4A1-AS1, miR-150-3p and/or SLCO4A1 were overexpressed or depleted in colon cancer cells to detect their effects on migration, invasion, sphere formation, apoptosis and tumorigenesis abilities of colon cancer stem CD133+CD44+ cells using both in vitro and in vivo assays. SLCO4A1-AS1 and SLCO4A1 were screened as the differentially expressed lncRNA and mRNA in colon cancer tissues. SLCO4A1-AS1 was confirmed to competitively bind to miR-150-3p to elevate SLCO4A1 expression. Moreover, knockdown of SLCO4A1-AS1 decreased SLCO4A1 expression, thus inhibiting cell migration, invasion, sphere formation, and tumorigenesis abilities and enhancing the apoptosis of CD133+CD44+ cells. Collectively, these findings provide evidence demonstrating that depleting SLCO4A1-AS1 competitively binds to miR-150-3p, which downregulates SLCO4A1 expression, thus hindering colon cancer progression.

LIM-Domain-Binding Protein 1 Mediates Cell Proliferation and Drug Resistance in Colorectal Cancer.

Objective: It has been shown that LIM-domain-binding protein 1 (LDB1) is involved in the tumorigenesis of several cancers, but its function in colorectal cancer (CRC) has not been fully explained. This study is aimed to investigate whether LDB1 is involved in regulating the cell growth and drug sensitivity of CRC. Methods: To analyze the protein expression of LDB1 in CRC tissues, western blot was used. KM plotter and UALCAN databases were used to predict the prognosis of CRC patients with low or high LDB1 expression. To do the correlation analysis in CRC tissues, GEPIA database was used. CCK-8 assay and xenograft models were used to evaluate the effects of LDB1 in CRC cell growth. An oxaliplatin-resistant cell line was constructed to evaluate the effect of LDB1 in drug sensitivity of CRC cells. Results: Our current research confirmed that LDB1 was upregulated in CRC tumor tissues, and its elevation predicted a poor prognosis for CRC patients. LDB1 was also found positively correlated with CCNA1, BCL2 and BCLW, but negatively correlated with the pro-apoptotic signals (BID, BAX and BAK). Silence of LDB1 significantly inhibited CRC cell growth in vitro, and CRC cells with low expression of LDB1 had a lower tumorigenesis rate in tumor-bearing nude mice. Our experiments also showed that LDB1 silence enhanced the anti-tumor activity of oxaliplatin in CRC cells. The expression of LDB1 was also found increased in oxaliplatin-resistant CRC cell lines, and silence of LDB1 partly restored the antitumor effect of oxaliplatin in an oxaliplatin-resistant CRC cell line. Conclusion: Our current results revealed the roles of LDB1 in the growth and drug resistance of CRC cells, and may provide the new theoretical support for LDB1 as a potential target for the treatment of CRC in the future.

Leukocyte-Mediated Combined Targeted Chemo and Gene Therapy for Esophageal Cancer.

Poor prognosis of esophageal cancer is associated with limited clinical treatment efficacy and lack of targeted therapies. With advances in nanomedicine, nanoparticle drug delivery systems play increasingly important roles in tumor treatment by enabling the simultaneous delivery of multiple therapeutic agents. We here propose a novel nanovector for targeted combination gene therapy and chemotherapy in esophageal cancer. A novel lipid nanovector (EYLN) was designed to carry the chemotherapy drug doxorubicin (Dox) and small interfering RNA against the lipid anabolic metabolism gene LPCAT1, which we previously showed to be significantly overexpressed in esophageal cancer tissues, and its interference inhibited the proliferation, invasion, and metastasis of esophageal cancer cells. This vector, EYLN-Dox/siLPCAT1, was further coated with leukocyte membranes to obtain mEYLNs-Dox/siLPCAT1. The particle size of the coated nanovector was approximately 136 nm, and the surface zeta potential was -21.18 mV. Compared with EYLNs-Dox/siLPCAT1, mEYLNs-Dox/siLPCAT1 were more easily internalized by esophageal cancer cells due to the LFA-1 highly expressed leukocyte membrane coating and showed significant inhibition of the proliferation, migration, and metastasis of esophageal cancer cells, along with their LPCAT1 expression, through more effective delivery of the drugs. Moreover, the nanovectors showed improved blood circulation time, tissue distribution, tumor targeting, and tumor suppression in a mouse model. Thus, combining chemo and gene therapy with this new nanodelivery system achieved greater therapeutic efficacy, providing a new strategy for the treatment of esophageal cancer.

Knockdown of TMEM45A overcomes multidrug resistance and epithelial-mesenchymal transition in human colorectal cancer cells through inhibition of TGF-ß signalling pathway.

Colorectal cancer (CRC), a leading cause of cancer death, has recently been known as the most prevalent malignancy worldwide. Although chemotherapy is an important therapeutic option for CRC patients, multidrug resistance (MDR) still remains a major cause of chemotherapy failure. Transmembrane protein 45A (TMEM45A) has been found highly expressed in various cancers, and is also proposed as an interesting biomarker for chemoresistance. However, the association between TMEM45A and MDR in CRC remains unclear. This study aimed to investigate the key role of TMEM45A in CRC by knockdown of its expression in 5-FU-resistant CRC cells (HCT-8/5-FU and SW480/5-FU) and their parental cells (HCT-8 and SW480). Data showed that TMEM45A was significantly up-regulated in HCT-8/5-FU and SW480/5-FU cells in comparison with their parental HCT-8 and SW480 cells. Knockdown of TMEM45A enhanced 5-FU sensitivity and 5-FU-induced apoptosis in HCT-8/5-FU and SW480/5-FU cells. It was also found that inhibition of TMEM45A increased the intracellular accumulation of Rhodamine-123 and down-regulated the expression of MDR1 in HCT-8/5-FU and SW480/5-FU cells. In addition, knockdown of TMEM45A suppressed migration and invasion of HCT-8/5-FU and SW480/5-FU cells. Furthermore, knockdown of TMEM45A not only attenuated MDR-enhanced epithelial-mesenchymal transition (EMT), but also suppressed MDR-enhanced activation of the TGF-ß signalling pathway in HCT-8/5-FU and SW480/5-FU cells. Taken together, our study suggests that knockdown of TMEM45A can effectively overcome MDR and inhibit EMT via suppression of the TGF-ß signalling pathway in human CRC cells, and that targeting TMEM45A will be a potential strategy in the treatment of MDR in CRC.

Long non-coding RNA LINC00858 exerts a tumor-promoting role in colon cancer via HNF4α and WNK2 regulation.

BACKGROUND: Long non-coding RNAs (lncRNAs) are known to be frequently dysregulated in many types of human cancer. As yet, however, their roles in colon carcinogenesis have not been fully elucidated. In the current study, we assessed whether lncRNA LINC00858 may be involved in the progression of colon cancer and, in addition, investigated its downstream targets. METHODS: LINC00858 expression in patient-derived colon cancer tissues and in colon cancer cell lines was determined using RT-qPCR. Also, relationships between LINC00858 expression and various clinicopathological characteristics were analyzed. The subcellular localization of LINC00858 was determined using fluorescence in situ hybridization. Interactions between LINC00858 and its downstream targets were first predicted by bioinformatic analysis and, subsequently, confirmed by RNA pull-down, RNA immunoprecipitation, chromatin immunoprecipitation and dual luciferase reporter assays. After in vitro upregulation of LINC00858 and/or silencing of WNK2 and hepatocyte nuclear factor 4α (HNF4α), the biological behavior of colon cancer cells was assessed using 5-ethynyl-2'-deoxyuridine (EdU) incorporation, Transwell invasion and tube formation assays. In vivo cancer growth was evaluated in nude mice. RESULTS: We found that LINC00858 was highly expressed in primary colon cancer tissues and colon cancer cell lines, and was mainly located in the nucleus. High LINC00858 expression was found to correlate with a poor differentiation, advanced TNM stages and lymph node metastasis. Exogenous overexpression of LINC00858 promoted cell proliferation, invasion and migration of colon cancer cells, and facilitated angiogenesis and tumor growth. In addition, we found that LINC00858 can bind to and upregulate the nuclear transcription factor HNF4α, leading to WNK2 expression downregulation. This, in turn, resulted in the promotion of colon cancer cell growth. CONCLUSIONS: From our data we conclude that LINC00858 acts as a tumor-promoting lncRNA in colon cancer by upregulating HNF4α and downregulating WNK2. Our results may provide novel targets for the treatment for colon cancer.

Mitotic checkpoint kinase Mps1/TTK predicts prognosis of colon cancer patients and regulates tumor proliferation and differentiation via PKCα/ERK1/2 and PI3K/Akt pathway.

Mps1/TTK plays an important role in development of many tumors. The purpose of the present study was designed to investigate the role of TTK in colon cancer. We analyzed TTK and colon cancer in the GEO database, colon cancer tissues and normal tissues were collected to verify the results by immunohistochemistry. We detected the TTK expression in the colon cancer cell lines, and overexpressed or silenced TTK expression in colon cancer cell lines. GEO database showed that the expression of TTK was higher in the colon cancer tissues than normal tissues, higher level of TTK shows unfavourable prognosis in colon patients. Furthermore, high differentiation of colon shows the lower expression of TTK. The higher expression of TTK links with the high microsatellite status. However, the expression of TTK has no significant difference among the different stages of colon cancer patients, and has no significant relationship with recurrence or relapse. Here, we also report that the differential expression of TTK in colon cancer cells alters the intrinsic negative regulation of cell proliferation and differentiation, resulting in the difference of proliferation and differentiation capacity. TTK could activate the PKCα/ERK1/2 to influence the proliferation and inactivate the PI3K/AKT pathway to inhibition the expression of MUC2 and TFF3 that related to the differentiation of colon cells. In conclusions, TTK promote the colon cancer cell proliferation via activation of PKCα/ERK1/2 and inhibit the differentiation via inactivation of PI3K/Akt pathway. TTK inhibition may be the potential therapeutic pathway for the treatment of colon cancer.

Overcoming Drug Resistance in Colon Cancer by Aptamer-Mediated Targeted Co-Delivery of Drug and siRNA Using Grapefruit-Derived Nanovectors.

BACKGROUND/AIMS: Multidrug resistance (MDR) is the most common cause of chemotherapy failure. Upregulation of P-glycoprotein (P-gp) is one of the main mechanisms underlying MDR. METHODS: In this study, we developed a targeted drug and small interfering (si)RNA co-delivery system based on specific aptamer-conjugated grapefruit-derived nanovectors (GNVs) that we tested in MDR LoVo colon cancer cells. The internalization of nanovectors in cancer cells was tested by fluorescence microscopy and flow cytometry. The anti-cancer activity in vitro was determined by colony formation and cell apoptosis assays. The biodistribution of nanovectors was analyzed by live imaging and the anti-cancer activity in vivo was observed. RESULTS: GNVs loaded with aptamer increased doxorubicin (Dox) accumulation in MDR LoVo cells, an effect that was abolished by pretreatment with DNase. The LA1 aptamer effectively promoted nanovector internalization into cells at 4°C and increased the targeted delivery of Dox to tumors. Constructs harboring Dox, LA1, and P-gp siRNA more effectively inhibited proliferation and enhanced apoptosis in cultured MDR LoVo cells while exhibiting more potent anti-tumor activity in vivo than free Dox or GNVs loaded with Dox alone or in conjunction with LA1, an effect that was associated with downregulation of P-gp expression. CONCLUSION: This GNV-based system may be an effective strategy for overcoming MDR in clinical settings.

Downregulation of RPN2 induces apoptosis and inhibits migration and invasion in colon carcinoma.

The morbidity of colorectal cancer (CRC) increases annualy, which accounts to higher mortality worldwide. Therefore, it is important to study the pathogenesis of colon cancer. Ribophorin II (RPN2), part of the N-oligosaccharyltransferase complex, is highly expressed in CRC. In the present study, we investigated whether RPN2 can regulate apoptosis, migration and invasion by RNA interference in CRC and sought to clarify the molecular mechanism involved. Based on previous research, an abnormal high expression of RPN2 was observed in CRC tissues and cell lines by real-time (RT)-PCR, immunohistochemistry (IHC) and western blot analysis. RPN2 knockdown via small RNA interference (siRNA) strategy attenuated the expression of RPN2 at the mRNA and protein levels in vivo, leading to decreased cell viability and increased cell apoptosis. In addition, RNAi-RPN2 effectively arrested the cell cycle at the G0/G1-phase in SW1116 and SW480 cells. Furthermore, the Transwell assay demonstrated that cell migration and invasion abilities were significantly inhibited after cell transfection with RPN2 interference plasmid. The apoptosis-related protein (caspase-3) expression was increased and the cell cycle-related protein (cyclin D1) expression was decreased in the siRNA-RPN2 group. RT-PCR and western blot analysis results indicated that migration- and invasion-related proteins including E-cadherin, matrix metalloproteinases (MMP)-2 and TIMP-2 were markedly regulated by RPN2 siRNA. Phosphorylation levels of signal transducer and activator of transcription (STAT)3 and Janus kinase (JAK)2 were inhibited by RPN2 siRNA. These findings indicated a novel pathway of tumor-promoting activity by RPN2 in CRC, with significant implications for unraveling the tumorigenesis of CRC.

Targeting PP2A activates AMPK signaling to inhibit colorectal cancer cells.

LB-100 is a novel PP2A inhibitor. Its activity in human colorectal cancer (CRC) cells was tested. The in vitro studies demonstrated that LB-100 inhibited survival and proliferation of both established CRC cells (HCT-116 and HT-29 lines) and primary human colon cancer cells. Further, LB-100 activated apoptosis and induced G1-S cell cycle arrest in CRC cells. LB-100 inhibited PP2A activity and activated AMPK signaling in CRC cells. AMPKα1 dominant negative mutation, shRNA-mediated knockdown or complete knockout (by CRISPR/Cas9 method) largely attenuated LB-100-induced AMPK activation and HCT-116 cytotoxicity. Notably, microRNA-17-92-mediated silence of PP2A (regulatory B subunit) also activated AMPK and induced HCT-116 cell death. Such effects were again largely attenuated by AMPKα mutation, silence or complete knockout. In vivo studies showed that intraperitoneal injection of LB-100 inhibited HCT-116 xenograft growth in nude mice. Its anti-tumor activity was largely compromised against HCT-116 tumors-derived from AMPKα1-knockout cells. We conclude that targeting PP2A by LB-100 and microRNA-17-92 activates AMPK signaling to inhibit CRC cells.

Delivery of a chemotherapeutic drug using novel hollow carbon spheres for esophageal cancer treatment.

Low toxicity and high efficacy are the key factors influencing the real-world clinical applications of nanomaterial-assisted drug delivery. In this study, novel hollow carbon spheres (HCSs) with narrow size distribution were developed. In addition to demonstrating their ease of synthesis for large-scale production, we also demonstrated in vitro that the HCSs possessed high drug-loading capacity, lower cell toxicity, and optimal drug release profile at low pH, similar to the pH in the tumor microenvironment. The HCSs also displayed excellent immunocompatibility and could rapidly distribute themselves in the cytoplasm to escape lysosomal clearance. More importantly, the HCSs could efficiently deliver doxorubicin (a representative chemotherapeutic drug) to tumor sites, which resulted in significant inhibition of tumor growth in an esophageal xenograft cancer model. This also prolonged the circulation time and altered the biodistribution of the drug. In conclusion, this study revealed a novel drug delivery system for targeted tumor therapy.

Prognostic role of microscopically positive margins for primary gastrointestinal stromal tumors: a systematic review and meta-analysis.

The impact and management of microscopically positive margins in gastrointestinal stromal tumors (GISTs) remain unclear. The aim of this study is to estimate the prognostic value of surgical margins for disease-free survival (DFS) and overall survival (OS) in patients with primary GISTs. Twelve studies with 1985 GIST patients were included. The overall recurrence rate in R1 resection and R0 resection group was 0.364 (95% CI 0.299-0.429) and 0.296 (95% CI 0.161-0.430), respectively. Meta-analysis confirmed that a microscopically positive margin could significantly impact the disease-free survival (HR 1.596, 95% CI 1.128-2.258; I(2) = 37.5%, P value = 0.091), but had no influence on overall survival (HR 1.430, 95% CI 0.608-3.363; I(2) = 60.8%, P value = 0.013). Importantly, subgroup analysis revealed that adjuvant imatinib treatment could attenuate the risk of recurrence for primary GIST patients who received R1 resection. (HR 1.308, 95% CI 0.583-2.935; I(2) = 53.2%, P value = 0.074). The level of evidence achieved in this study was "moderate" for DFS and "low" for OS. In conclusion, this study revealed that a microscopically positive margin is an unfavorable prognostic factor for GIST patients with R1 resection, and adjuvant imatinib treatment is proved to be effective.

MiR-874 promotes intestinal barrier dysfunction through targeting AQP3 following intestinal ischemic injury.

Intestinal ischemic injury is a significant clinical problem arising from diseases or as a complication of abdominal surgery. Our previous study showed aquaporin 3 is involved in intestinal barrier impairment. Here, we revealed that intestinal ischemia induced a time-dependent increase of miR-874 expression and a time-dependent decrease of AQP3 expression, and the level of miR-874 expression was inversely related to AQP3 protein expression. In addition, miR-874 promoted the paracellular permeability in vitro through targeting 3'UTR of AQP3. Two of the tight junction proteins, Occludin and Claudin-1, were found to be involved in miR-874-induced intestinal barrier dysfunction.

miR-874 Inhibits cell proliferation, migration and invasion through targeting aquaporin-3 in gastric cancer.

BACKGROUND: Aquaporin-3 (AQP3) is a water transporting protein which plays an oncogenic role in several malignant tumors. However, its regulatory mechanism remains elusive to date. In this study, we investigated the microRNA-mediated gene repression mechanism involved in AQP3's role. METHODS: The potential microRNAs targeting AQP3 were searched via bioinformatic methods and identified by luciferase reporter assays, microRNA RT-PCR and western blotting. The expression patterns of miR-874 and AQP3 in human gastric cancer (GC) specimens and cell lines were determined by microRNA RT-PCR and western blotting. 5-ethynyl-2'-deoxyuridine, cell migration and invasion assays and tumorigenicity in vivo were adopted to observe the effects of miR-874 depletion or ectopic miR-874 expression on GC cell phenotypes. Cell apoptosis was evaluated by FACS and TUNEL in vitro and in vivo respectively. RESULTS: miR-874 suppressed AQP3 expression by binding to the 3'UTR of AQP3 mRNA in GC cells. miR-874 was significantly down-regulated and reversely correlated with AQP3 protein levels in clinical samples. Analysis of the clinicopathological significance showed that miR-874 and AQP3 were closely correlated with GC characteristics. Functional analyses indicated that ectopic miR-874 expression suppressed the growth, migration, invasion and tumorigenicity of GC cells, whereas miR-874 knockdown promoted these phenotypes. Down-regulation of Bcl-2, MT1-MMP, MMP-2 and MMP-9 and upregulation of caspase-3 activity and Bax were involved in miR-874 inducing cell apoptosis, and inhibiting migration and invasion. CONCLUSIONS: These results provide a mechanism by which AQP3 is upregulated, as well as highlight the importance of miR-874 in gastric cancer development and progression.