ALKBH5 promotes hepatocellular carcinoma cell proliferation, migration and invasion by regulating TTI1 expression.

The objective of this research was to investigate the potential mechanisms of AlkB homolog 5, RNA demethylase (ALKBH5) in hepatocellular carcinoma (HCC). We used The Cancer Genome Atlas (TCGA), Kruskal-Wallis method and Kaplan-Meier (KM) survival analysis to study the expression of ALKBH5 and its correlation with clinical factors in HCC. In vitro experiments verified the expression of ALKBH5 and its effect on HCC cell phenotype. We screened differentially expressed genes (DEGs) from HCC patients associated with ALKBH5. Through this screening we identified the downstream gene TTI1 which is associated with ALKBH5 and investigated its function using Gene Expression Profiling Interaction Analysis (GEPIA) along with univariate Cox proportional hazards regression analysis. Finally, we analyzed the functions of ALKBH5 and TTI1 in HCC cells. Across numerous pan-cancer types, we observed significant overexpression of ALKBH5. In vitro experiments confirmed ALKBH5 as an oncogene in HCC, with its knockdown leading to suppressed cell proliferation, migration, and invasion. Bioinformatics analyses also demonstrated a significant positive correlation between ALKBH5 and TTI1. TTI1, highly expressed in cells, showed promising prognostic ability for patients. Further experiments confirmed that suppressing TTI1 impeded cell growth and movement, with this effect partially offset by increased ALKBH5 expression. Conversely, promoting these cellular processes was observed with TTI1 overexpression, but was dampened by decreased ALKBH5 expression. In conclusion, our findings suggest that ALKBH5 may influence proliferation, migration and invasion of HCC by modulating TTI1 expression, providing a new direction for treating HCC.

Gut microbiota alteration after cholecystectomy contributes to post-cholecystectomy diarrhea via bile acids stimulating colonic serotonin.

Post-cholecystectomy diarrhea (PCD) is highly prevalent among outpatients with cholecystectomy, and gut microbiota alteration is correlated with it. However, how and to what extent changed fecal bacteria contributes to diarrhea are still unrevealed. Humanized gut microbiome mice model by fecal microbiota transplantation was established to explore the diarrhea-inducible effects of gut microbiota. The role of microbial bile acids (BAs) metabolites was identified by UPLC/MS and the underlying mechanisms were investigated with selective inhibitors and antagonists as probes. These mice transplanted with fecal microbiome of PCD patients (PCD mice) exhibited significantly enhanced gastrointestinal motility and elevated fecal water content, compared with these mice with fecal microbiome of NonPCD patients and HC. In analyzing gut microbiota, tryptophan metabolism was enriched in PCD microbiome. In addition, overabundant serotonin in serum and colon, along with elevated biosynthesis gene and reduced reuptake gene, and highly expressed 5-HT receptors (5-HTRs) in colon of PCD mice were found, but not in small intestine. Notably, diarrheal phenotypes in PCD mice were depleted by tryptophan hydroxylase 1 inhibitor (LX1606) and 5-HTRs selective antagonists (alosetron and GR113808). Furthermore, increased microbial secondary BAs metabolites of DCA, HDCA and LCA were revealed in feces of PCD mice and they were found responsible for stimulating 5-HT level in vitro and in vivo. Intriguingly, blocking BAs-conjugated TGR5/TRPA1 signaling pathway could significantly alleviate PCD. In conclusion, altered gut microbiota after cholecystectomy contributes to PCD by promoting secondary BAs in colon, which stimulates colonic 5-HT and increases colon motility.

Effect of aging on acute pancreatitis through gut microbiota.

Background: Compared to younger people, older people have a higher risk and poorer prognosis of acute pancreatitis, but the effect of gut microbiota on acute pancreatitis is still unknown. We aim to investigate the effect of aging gut microbiota on acute pancreatitis and explore the potential mechanism of this phenomenon. Methods: Eighteen fecal samples from healthy adult participants, including nine older and nine younger adults were collected. C57BL/6 mice were treated with antibiotics for fecal microbiota transplantation from older and younger participants. Acute pancreatitis was induced by cerulein and lipopolysaccharide in these mice. The effect of the aged gut microbiota was further tested via antibiotic treatment before or after acute pancreatitis induction. Results: The gut microbiota of older and younger adults differed greatly. Aged gut microbiota exacerbated acute pancreatitis during both the early and recovery stages. At the same time, the mRNA expression of multiple antimicrobial peptides in the pancreas and ileum declined in the older group. Antibiotic treatment before acute pancreatitis could remove the effect of aging gut microbiota, but antibiotic treatment after acute pancreatitis could not. Conclusion: Aging can affect acute pancreatitis through gut microbiota which characterizes the deletion of multiple types of non-dominant species. This change in gut microbiota may potentially regulate antimicrobial peptides in the early and recovery stages. The level of antimicrobial peptides has negative correlations with a more severe phenotype.

Disordered Gut Microbiota Correlates With Altered Fecal Bile Acid Metabolism and Post-cholecystectomy Diarrhea.

Post-cholecystectomy diarrhea (PCD) is a common complication of gallbladder removal, and gut microbiota changes have been determined in PCD patients. Bile acid diarrhea (BAD) is supposed to be the main pathogenic factor for PCD due to the disrupted fecal bile acid metabolism in diarrheal patients. However, the profiling of bile acid metabolite alteration in PCD is unclear and whether changed gut microbiota and fecal bile acid metabolism are correlated is also underdetermined. The fecal bile acid metabolites from fecal samples were profiled by targeted UPLC/MS (ultra-high-performance liquid chromatography coupled with a triple-quadrupole mass spectrometer) and the composition of fecal bile acid metabolites in PCD patients was demonstrated to be distinct from those in Non-PCD and HC groups. In addition, the quantification of bile acid excretion in feces of diarrheal patients was significantly elevated. Furthermore, 16S rRNA sequencing results revealed that PCD patients had the lowest operational taxonomic units (OTU) and significant reduction in microbial richness and evenness. Bacterial composition was remarkably shifted in PCD patients, which mainly lay in dominated phyla Firmicutes and Bacteroidota. Besides, the co-abundance network among genus bacteria declined in PCD. Among the genera, Prevotella, Enterococcus, and Erysipelotrichaceae_UCG-003 were enriched, but Alistipes, Bacteroides, Ruminococcus, and Phascolarctobacterium were reduced. Moreover, these disease-linked genera were closely associated with several diarrheal phenotypes. Notably, changed bile acid metabolites exhibited strong correlations with gut microbiota as well. Conclusively, this study reveals associations between PCD-linked microbes and bile acid metabolites, which may synergistically correlate to postoperative diarrhea.

SLC41A3 Exhibits as a Carcinoma Biomarker and Promoter in Liver Hepatocellular Carcinoma.

Liver Hepatocellular Carcinoma (LIHC) is the fifth widely occurred carcinoma, which is thought to be the second primary contributor of carcinoma-associated death. There are almost 788,000 death tolls worldwide. Solute carrier family 41 member 3 (SLC41A3) is a member of solute carrier family 41, and it is the key point of numerous researches. Our research attempted to explore the links between SLC41A3 and LIHC through public databases. Higher expression of SLC41A3 displayed an intimate association with higher pathological stages and poorer prognosis. GO and KEGG analysis revealed the possible regulatory pathways of SLC41A3. Additionally, we carried out cell functional experiments to determine the expression of SLC41A3 in the cell lines of LIHC, as well as the effects of its silence on cell proliferation, migration, and invasion. Our data showed that SLC41A3 was greatly increased in the cell lines of LIHC. Moreover, silencing SLC41A3 impeded LIHC cell proliferation, migration, and invasion in vitro. Collectively, our study demonstrated that highly expressed SLC41A3 was a probable indication of LIHC occurrence, and SLC41A3 could be regarded as a prospective target in the treatment of LIHC.

RORγt inhibitor SR1001 alleviates acute pancreatitis by suppressing pancreatic IL-17-producing Th17 and γδ-T cells in mice with ceruletide-induced pancreatitis.

The management of acute pancreatitis (AP) remains a challenge to clinicians worldwide for limited effective interventions. Retinoid orphan receptor gamma t (RORγt) is a therapeutic target for several diseases; however, it is unclear whether inhibiting RORγt can ameliorate AP. The relative expression of RORγt, IL-17 and IL-23 in the peripheral blood mononuclear cells of AP patients was measured by RT-PCR. An AP mouse model was induced by ceruletide, and SR1001 was injected before ceruletide administration. RORγt+ cells, T helper 17 cells (Th17), regulatory T cells (Tregs) and γδ T cells were assessed in the pancreas and spleen by flow cytometry. Higher RORγt expression in patients indicated the potential role of RORγt in AP progression. Analyses of the IL-17/IL-23 axis confirmed its role. SR1001 significantly alleviated AP histologically in the mouse model. Serum levels of amylase, IL-6, TNFalpha, IL-17 and IL-23 decreased upon SR1001 treatment. SR1001 selectively decreased the number of RORγt+, Th17, Tregs and γδ T cells in the pancreas but not the spleen. Collectively, these results showed that SR1001 exerted therapeutic effects on AP by suppressing IL-17-secreting Th17 and γδ T cells in the pancreas. Thus, SR1001 may be a promising drug for the treatment of AP in the clinic.

Role of Asxl2 in non­alcoholic steatohepatitis­related hepatocellular carcinoma developed from diabetes.

The present study investigated the mechanism(s) of non­alcoholic steatohepatitis­related hepatocellular carcinoma (NASH­HCC) developed from diabetes. Streptozotocin and a high­fat diet (STZ­HFD) were used to induce NASH­HCC in ApoE­/­ mice. Mouse liver functions were evaluated by H&E staining, liver/body weight and serum biochemical analysis. The expression levels of inflammation­associated factors were determined by RT­qPCR. Gene expression profiles related to molecular functions and pathways of NASH­HCC were examined by principal component analysis, heatmap, gene ontology and KEGG pathway enrichment analysis. Differentially expressed genes (DEGs) in tumor tissues were confirmed by RT­qPCR. The expression of Asxl2 in human NASH­HCC, other HCC tissues and HCC cells was measured by western blot (WB analysis) and RT­qPCR. For SNU­182 cells transfected with siAsxl2 or Hep3B cells with Asxl2 overexpression, cell proliferation, cell cycle, migration and invasion were respectively determined by CCK­8 assays, flow cytometry, wounding healing and Transwell assays. The expression levels of cell metastasis­ and cycle­related proteins were determined by WB analysis and RT­qPCR. NASH­HCC model mice exhibited tumor protrusion with severe steatosis. The blood glucose concentration, serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and low­density lipoprotein (LDL), total bile acid (TBA) and the levels of interleukin (IL)­6, tumor necrosis factor (TNF)­α, glypican 3 (GPC3) and transforming growth factor (TGF)­ß were all increased in NASH­HCC model mice. DEGs were mainly related to chromosome organization, the cell cycle and the mitogen­activated kinase (MAPK) pathway. Asxl2 was significantly downregulated in HCC tissues and cells, and this regulated cell growth, migration and invasion. The gene expression pattern, related molecular functions and signaling pathways of NASH­HCC differed from those of normal liver tissues. Additionally, the downregulation of Asxl2 may play a potential role in development of NASH­HCC in patients with diabetes.

LncRNA MYLK-AS1 facilitates tumor progression and angiogenesis by targeting miR-424-5p/E2F7 axis and activating VEGFR-2 signaling pathway in hepatocellular carcinoma.

BACKGROUND: Long non-coding RNAs (lncRNAs) are crucial in the invasion, angiogenesis, progression, and metastasis of hepatocellular carcinoma (HCC). The lncRNA MYLK-AS1 promotes the growth and invasion of HCC through the EGFR/HER2-ERK1/2 signaling pathway. However, the clinical significance of MYLK-AS1 in HCC still needs to be further determined. METHODS: Bioinformatic analysis was performed to determine the potential relationship among MYLK-AS1, miRNAs and mRNAs. A total of 156 samples of normal liver and paired HCC tissues from HCC patients were used to evaluate MYLK-AS1 expression by qRT-PCR. Human HCC cell lines were used to evaluate the colony formation, cell proliferation, migration, invasion, cell cycle and apoptosis after transfection of lentiviral short-hairpin RNAs (shRNAs) targeting MYLK-AS1 or MYLK-AS1 vectors. The competitive endogenous RNA (ceRNA) mechanism was clarified using fluorescence in situ hybridization (FISH), Western blotting, qPCR, RNA binding protein immunoprecipitation (RIP), and dual luciferase reporter analysis. RESULTS: MYLK-AS1 up-regulation was detected in the HCC tumor tissues and cell lines associated with the enhancement of the angiogenesis and tumor progression. The down-regulation of MYLK-AS1 reversed the effects on angiogenesis, proliferation, invasion and metastasis in the HCC cells and in vivo. MYLK-AS1 acted as ceRNA, capable of regulating the angiogenesis in HCC, while the microRNA miR-424-5p was the direct target of MYLK-AS1. Promoting the angiogenesis and the tumor proliferation, the complex MYLK-AS1/miR-424-5p activated the VEGFR-2 signaling through E2F7, whereas the specific targeting of E2F transcription factor 7 (E2F7) by miR-424-5p, was indicated by the mechanism studies. CONCLUSIONS: MYLK-AS1 and E2F7 are closely related to some malignant clinicopathological features and prognosis of HCC, thus the MYLK-AS1/ miR-424-5p/E2F7 signaling pathway might represent a promising treatment strategy to combat HCC.

Erratum: Up-regulation of LINC00161 correlates with tumor migration and invasion and poor prognosis of patients with hepatocellular carcinoma.

[This corrects the article DOI: 10.18632/oncotarget.17040.].

Cross-talk among AFAP1-AS1, ACVR1 and microRNA-384 regulates the stemness of pancreatic cancer cells and tumorigenicity in nude mice.

BACKGROUND: Pancreatic cancer (PC) represents one of the most aggressive forms of cancer. The role of long non-coding RNAs (lncRNAs) has been highlighted in various malignancies including PC. The aim of the present study was to investigate the effects associated with actin filament-associated protein 1 antisense RNA 1 (AFAP1-AS1) on the progression of PC and the underlying mechanism. METHODS: Microarray-based gene expression profiling of PC was performed to identify PC-related lncRNAs, after which the expression of AFAP1-AS1 and cancer stem cell (CSC) markers in PC tissues and cells were determined accordingly. The potential microRNA-384 (miR-384) capable of binding to AFAP1-AS1, in addition to its ability to regulate activin receptor A type I (ACVR1) were analyzed. In order to investigate the effect of the AFAP1-AS1/miR-384/ACVR1 axis on self-renewal ability, tumorigenicity, invasion, migration and stemness of PC cells, shRNA-AFAP1-AS1, miR-384 mimic and inhibitor were cloned into cells. RESULTS: High expression of AFAP1-AS1 and ACVR1 with low expression of miR-384 were detected in PC tissues. ACVR1 was determined to be down-regulated when miR-384 was overexpressed, while the inhibition of AFAP1-AS1 decreased its ability to binding competitively to miR-384, resulting in the down-regulation of ACVR1 and enhancing miR-384 expression, ultimately inhibiting the progression of PC. The knockdown of AFAP1-AS1 or overexpression of miR-384 was confirmed to impair PC cell self-renewal ability, tumorigenicity, invasion, migration and stemness. CONCLUSIONS: Taken together, AFAP1-AS1 functions as an endogenous RNA by competitively binding to miR-384 to regulate ACVR1, thus conferring inhibitory effects on PC cell stemness and tumorigenicity.

Total flavonoid aglycones extract in Radix Scutellariae induces cross-regulation between autophagy and apoptosis in pancreatic cancer cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Radix Scutellariae (RS), the dried root of Scutellariae baicalensis Georgi, known as a herbal medicine in several Asian countries including China, has been widely used to treat inflammation, hypertension, cardiovascular disease as well as cancer. The total flavonoid aglycone extracted (TFAE) was extracted by ethyl acetate and this extraction methodology was optimized and obtained the protection of Chinese patents. AIM OF THE STUDY: To investigate the underlying mechanism of the chemotherapeutic effects of TFAE in inducing autophagy and apoptosis in pancreatic cancer cells in vitro and in vivo. MATERIALS AND METHODS: We performed CCK8 assays, AnnexinV-FITC/PI staining, flow cytometry assays, transmission electron microscopy, immunofluorescence analysis and Western blot to study the molecular mechanism of TFAE in inducing autophagy and apoptosis in pancreatic cancer cells in vitro and in vivo. RESULTS: In vitro, TFAE exhibits significant anti-tumor activity against pancreatic cancer cell lines, especially for BxPC3 (IC50 = 6.5 µg mL-1). Moreover, TFAE induces apoptosis and autophagy as evidenced by the increased apoptosis or autophagy-related protein level, the increased the fraction of apoptotic cells and the punctuate patterns of LC3 II. Furthermore, TFAE induce autophagy through PI3K/Akt/mTOR inhibition. Interestingly, pharmacological block autophagy by 3-MA enhanced TFAE-induced apoptosis, indicating that TFAE induced autophagy functions as a cytoprotective process against apoptosis. In vivo, 150 mg/kg TFAE inhibited the BxPC3 tumor growth in immune deficient mice with the inhibitory rate of 66.87% and induced both apoptosis and autophagy. CONCLUSION: TFAE have anti-tumor activity against pancreatic cancer and can induce apoptosis and autophagy through PI3K/Akt/mTOR signal pathway. TFAE might be a potential anticancer drug to be further developed for human pancreatic cancer therapy.

The association between preoperative serum interleukin-6 levels and postoperative prognosis in patients with T2 gallbladder cancer.

BACKGROUND: Interleukin-6 (IL-6) is closely associated with tumor progression. Whether it can predict postoperative prognosis of patients with T2 gallbladder cancer (GBC) remains controversial. METHODS: We retrospectively collected the medical records of 125 patients with T2 GBC. Then, we analyzed the association between preoperative serum IL-6 levels and postoperative survival by multivariate Cox analyses and Kaplan-Meier curves in exploratory subgroups. RESULTS: Predictive effects of serum IL-6 levels on overall survival were similar across most of the evaluated subgroups, except in different tumor location subgroups. The independent odds ratio (OR) of serum IL-6 levels was 2.57 (95%CI 1.73-3.82) in the hepatic side subgroup, while it was 1.15 (95%CI 0.68-1.93) in the peritoneal side subgroup (P = 0.014 for interaction). When we categorized serum IL-6 levels by median value (4.2 pg/mL), the 5-year survival rate of patients with high serum IL-6 levels was significantly higher in the hepatic side subgroup (58.5% vs 14.8%, P < 0.001), but no such difference was found in the peritoneal side subgroup (62.2% vs 67.6%, P = 0.722). CONCLUSIONS: Preoperative serum IL-6 is significantly associated with prognostic implications in patients with hepatic side T2 GBC, not in those with peritoneal side tumors.

Gypenosides Reduced the Risk of Overweight and Insulin Resistance in C57BL/6J Mice through Modulating Adipose Thermogenesis and Gut Microbiota.

This study investigated whether and how gypenosides from jiaogulan tea at 100 and 300 mg/kg/day levels could reduce the development of overweight and insulin resistance in C57 BL/6J mice fed a high-fat diet in 12 weeks. The 300 mg/kg/day gypenosides supplement significantly reduced final body weight, plasma total cholesterol, and homeostasis model assessment-estimated insulin resistance (HOMA-IR) index by 19.9%, 40%, and 36%, respectively, compared with the high-fat diet control group. Gypenosides also increased brown adipocyte tissue activity and white adipose tissue browning. The expression of genes involved in mitochondrial activity and fatty acid ß-oxidation were also increased in both brown and white adipocyte tissues. In addition, gypenosides at 100 and 300 mg/kg/day levels decreased the ratio of Firmicutes to Bacteroidetes by 20% and 58.6%, respectively, and increased Akkermansia muciniphila abundance in the gut microbiota.

Up-regulation of LINC00161 correlates with tumor migration and invasion and poor prognosis of patients with hepatocellular carcinoma.

Accumulating evidence suggested that long non-coding RNAs (lncRNAs) play essential roles in various biological processes, including tumorigenesis. Aberrant expression of LINC00161 has been reported in some cancer types, however, the association of LINC00161 and hepatocellular carcinoma (HCC) has not been evaluated. Here, we measured the expression of LINC00161 in HCC tissues and corresponding normal liver tissues using real-time PCR. The result showed that the expression level of LINC00161 was significantly higher in HCC tissues. Further analysis indicated that HCC patients with higher LINC00161 expression have shorter survival. Multivariate Cox regression analysis showed that LINC00161 expression was an independent prognostic factor for the overall survival. Furthermore, our result indicated that knock-down of LINC00161 can significantly inhibit liver cancer cell migration and invasion. The present work indicated that LINC00161 might serve as an oncogenic gene and play a pivotal role in promoting tumor migration and invasion in HCC. Our work implicates the promising effect of LINC00161 on the prognosis of HCC.

A five-long non-coding RNA signature to improve prognosis prediction of clear cell renal cell carcinoma.

Recent works have reported that long non-coding RNAs (lncRNAs) play critical roles in tumorigenesis and prognosis of cancers, suggesting the potential utility of lncRNAs as cancer prognostic markers. However, lncRNA signatures in predicting the survival of patients with clear cell renal cell carcinoma (ccRCC) remain unknown. In this study, we attempted to identify lncRNA signatures and their prognostic values in ccRCC. Using lncRNA expression profiling data in 440 ccRCC tumors from The Cancer Genome Atlas (TCGA) data, a five-lncRNA signature (AC069513.4, AC003092.1, CTC-205M6.2, RP11-507K2.3, U91328.21) has been identified to be significantly associated with ccRCC patients' overall survival in both training set and testing set. Based on the lncRNA signature, ccRCC patients could be divided into high-risk and low-risk group with significantly different survival rate. Further multivariable Cox regression analysis suggested that the prognostic value of this signature was independent of clinical factors. Functional enrichment analyses showed the potential functional roles of the five prognostic lncRNAs in ccRCC oncogenesis. These results indicated that this five-lncRNA signature could be used as an independent prognostic biomarker in the prediction of ccRCC patients' survival.

Inhibitory Effect of Piceatannol on TNF-α-Mediated Inflammation and Insulin Resistance in 3T3-L1 Adipocytes.

Piceatannol, a bioactive component in grape and blueberry, was examined for its potential in decreasing the inflammatory activities in adipocytes using a cocultured adipocyte and macrophage system, and suppressing tumor necrosis factor-α (TNF-α)-mediated inflammation and the related insulin resistance using a 3T3-L1 adipocyte model. Piceatannol at 10 µM significantly reduced the release of inflammatory cytokines of TNF-α and monocyte chemoattractant protein-1 (MCP-1) by 19 and 31% in the cocultured system, respectively. Pretreatment with piceatannol also inhibited TNF-α-induced expression of interleukin-6 (IL-6) and MCP-1 at both mRNA and protein levels in the 3T3-L1 adipocytes. Piceatannol also partially improved the malfunction of insulin-stimulated glucose uptake, which was reduced by TNF-α in 3T3-L1 adipocytes. Furthermore, the inhibitions were mediated by significant blocking of IκBα phosphorylation and nuclear factor-κB (NF-κB) activation through suppressing nuclear translocation of NF-κB p65 along with c-Jun N-terminal kinase (JNK)-mitogen activated protein kinase (MAPK) activation. In addition, the Akt-dependent forkhead box O1 (FoxO1) signaling pathway was involved in the restoration of insulin-stimulated glucose uptake through suppressing the down-regulation of phosphorylation of Akt and FoxO1 expressions. These results suggested the potential of piceatannol in improving chronic inflammatory condition and insulin sensitivity in obese adipose tissues.

Ubiquitin-conjugating enzyme UbcH10 promotes gastric cancer growth and is a potential biomarker for gastric cancer.

Gastric cancer is a fatal disease and the availability of early diagnostic methods is limited. There is an urgent need to identify effective targets for early diagnosis and therapeutics. UbcH10 is a ubiquitin-conjugating enzyme with high expression in various types of cancers. In the present study, several gastric tumor cell lines with high or low expression of UbcH10 were exploited to study the role of UbcH10 in gastric cancer. Knockdown of UbcH10 expression using siRNA in gastric cancer cell lines with high expression of UbcH10 resulted in reduced proliferation, increased cisplatin-induced apoptosis and reduced serum-induced ERK, Akt and p38 phosphorylation signaling. In agreement, overexpression of UbcH10 in gastric cancer cell lines with low expression of UbcH10 led to enhanced cell proliferation and resistance to cisplatin-induced apoptosis. Most importantly, IHC analyses showed that the UbcH10 protein was expressed at a high level in most patient gastric cancer tissues, but was absent in adjacent mesenchyme tissues. These data suggest that UbcH10 may promote gastric cancer growth and can serve as a biomarker for diagnosis or as a target for novel therapeutics in gastric cancer.