S100A8-Mediated Inflammatory Signaling Drives Colorectal Cancer Progression via the CXCL5/CXCR2 Axis.

Background: S100A8/S100A9 belong to the S100 calcium-binding protein family and play an essential role in the progression of chronic inflammation in diseases. It also regulates various biological processes such as tumor cell survival, apoptosis, and invasive metastasis. The extracellular form of S100A8/S100A9 functions by modulating cellular oxidative metabolism and facilitating inflammation-to-cancer progression. This modulation occurs through specific binding to receptors like RAGE and TLR4 and activation of signaling pathways including STAT3 and NF-κB. In tumor cells, S100A8 and S100A9 induce phenotypic changes by influencing calcium ion concentrations and other pathways. However, the precise function of high S100A8/S100A9 expression in colorectal cancer cells remains unclear. Methods: To explore the role of S100A8/S100A9 in colorectal cancer, we used immunohistochemistry and data from GEO and TCGA databases to analyze its expression in colorectal cancer cells, normal intestinal mucosa, and adjacent tissues. Functional models of high S100A8/S100A9 expression in colorectal cancer cells were established through transfection with overexpression plasmids. Protein microarrays, enzyme-linked immunosorbent assays (ELISAs), and real-time PCR were employed to assess the expression and secretion of 40 cytokines. MTT and Transwell invasion assays were conducted to evaluate changes in cell proliferation, invasion, and chemotaxis. Finally, tail vein and subcutaneous tumorigenesis assays assessed cell proliferation and migration in vivo. Results: We observed significantly higher expression of S100A8/S100A9 in colorectal cancer epithelial cells compared to normal intestinal mucosa and adjacent tissues. Overexpression of S100A8/S100A9 in mouse colon cancer cells CT26.WT led to differential increases in the secretion levels of various cytokines (CXCL5, CXCL11, GM-CSF, G-CSF, IL1a, IL1b, sTNF RI, and CCL3). Additionally, this overexpression activated signaling pathways such as STAT3, NF-κB, and ERK-MAPK. The synthesis and secretion of inflammatory factors could be inhibited by using NF-κB and ERK-MAPK pathway inhibitors. Moreover, S100A8 promotes the proliferation and invasion of colon cancer cells. Notably, the CXCR2 inhibitor (SB265610) effectively reversed the phenotypic changes induced by the CXCL5/CXCR2 biological axis. Conclusions: Our findings indicate that increased expression of S100A8 and S100A9 in colon cancer epithelial cells enhances the secretion of inflammatory factors by activating NF-κB, ERK-MAPK, and other signaling pathways. S100A8 facilitates colon cancer cell proliferation, invasion, and metastasis through the CXCL5/CXCR2 biological axis.

Histone deacetylase (HDAC) 11 inhibits matrix metalloproteinase (MMP) 3 expression to suppress colorectal cancer metastasis.

Emerging evidence has implicated invasion and metastasis are the major common reason of treatment failure and the leading cause of death in colorectal cancer (CRC). Many members of the HDAC family have been reported to be key factors in the genesis and progression of cancer. Until now, few research focused on the actual expression patterns of HDAC11 in most malignancies. In the current study, we found that the expression of HDAC11 is decreased in mouse colitis tissues and colitis-associated cancer (CAC) tissue compared with normal colon tissue. Clinically HDAC11 expression is significantly lower in colorectal cancer tissues of patients and correlated with lymph node metastasis. Additionally, HDAC11 is downregulated in the relative high metastatic potential colorectal cancer cells. We also found HDAC11 inhibits the migration and invasion of colorectal cancer cell by downregulating Mmp3 expression. At the molecular level, the expression of HDAC11 inversely correlated with the level of histone H3K9 and H3K14 acetylation. In addition, analysis of chromatin-protein association by ChIP-qPCR demonstrated that the level of H3K9 acetylation correlated with the upregulation of Mmp3. Through a better understanding of this previously unknown role of HDAC11 in migration and invasion of colorectal cancer, HDAC11 may become a novel candidate for developing rational therapeutic strategies.

Proinflammatory S100A8 Induces PD-L1 Expression in Macrophages, Mediating Tumor Immune Escape.

S100A8 is a damage-associated molecular pattern protein released by monocytes, playing a decisive role in the development of inflammation. Nonresolving inflammation is viewed as a driving force in tumorigenesis, and its role in tumor immune escape also attracted attentions. PD-1/PD-L1 axis is a critical determinant of physiological immune homeostasis, and anti-PD-1 or PD-L1 therapy has becoming the most exciting field of oncology. Multiple regulation mechanisms have been contributed to PD-L1 expression modulation including inflammatory mediators. In this study we reported that S100A8 significantly induced PD-L1 expression in monocytes/macrophages but not in tumor cells. S100A8 induced PD-L1 transcription through the TLR4 receptor and multiple crucial pathways of inflammation process. S100A8 modulated the histone modification of the PD-L1 promoter in monocytes/macrophages. S100A8-pretreated macrophages had immunosuppressive function and attenuated the antitumor ability of CTLs both in vitro and in vivo. A highly positive correlation existed between S100A8 expression and PD-L1 expression in human cancer specimens. To our knowledge, our study uncovers a novel molecular mechanism for regulating PD-L1 transcription by an inflammatory mediator S100A8, and reveals the importance of comprehensive understanding the role of inflammation in tumorigenesis as well as in tumor immune escape.

Changes in the intestinal microecology induced by bacillus subtilis inhibit the occurrence of ulcerative colitis and associated cancers: a study on the mechanisms.

This study aimed to explore how changes in intestinal floras caused by Bacillus subtilis (Bs) inhibited occurrence of ulcerative colitis (UC) and associated cancers. Bs was used as an intervention in an azoxymethane (AOM)/dextran sodium sulfate sodium (DSS) animal model. Stool specimens were analyzed for changes in intestinal floras. Disease activity index (DAI) scores, body mass indices, cancer counts, and other indices were calculated, while changes in the colon mucosa were observed. Compared with AOM/DSS group, carcinogenesis significantly reduced and intestinal inflammations and DAI score alleviated; diversity, evenness, and number of species of floras significantly increased; and relative abundances of Rikenellaceae and Lactobacillus increased when UC developed into cancers in the AOM/DSS + Bs group. Colon epitheliums in the mice were severely damaged in the AOM/DSS group, while mucosae were repaired in the AOM/DSS + Bs group. The mRNA expression levels of IL-6 and IL-17a were lower while those of IL-10 and TGF-ß1 were higher, and the expression level of Ki-67 decreased while that of caspase 3 increased in the AOM/DSS + Bs group. Bs intervention could alter the structure of intestinal floras, repair the mucosal barrier, adjust immunity, and reduce the incidence of cancer in the AOM/DSS animal model.

Correction to: Evaluation of 22G fine-needle aspiration (FNA) versus fine-needle biopsy (FNB) for endoscopic ultrasound-guided sampling of pancreatic lesions: a prospective comparison study.

The HTML version of this article was updated to indicate that the copyright is with The Author(s).

Inhibition of lncRNA NEAT1 suppresses the inflammatory response in IBD by modulating the intestinal epithelial barrier and by exosome-mediated polarization of macrophages.

Inflammatory bowel disease (IBD) is a multifactorial inflammatory disease, and increasing evidence has demonstrated that the mechanism of the pathogenesis of IBD is associated with intestinal epithelial barrier injury. Long non­coding RNAs (lncRNAs) are a class of transcripts >200 nucleotides in length with limited protein­coding capability. Nuclear paraspeckle assembly transcript 1 (NEAT1) is a recently identified nuclear­restricted lncRNA, which localizes in subnuclear structures, termed paraspeckles, and is involved in the immune response in a variety of ways. However, the function of NEAT1 in IBD remains to be fully elucidated. In the present study, reverse transcription­quantitative polymerase chain reaction assays were performed to determine the expression levels of NEAT1 lncRNA in IBD serum samples and tissues. Furthermore, the effect of NEAT1 on the cell permeability of colon cells was investigated via determination of trans­epithelial electrical resistance as well as performance of western blot and immunofluorescence assays. In addition, dextran sodium sulfate assays were performed to investigate the effect of downregulation of NEAT1 in IBD of mice. The present study detected the expression levels of NEAT1 in IBD cells and animal models to examine the changes in intestinal epithelial cell permeability following inhibition of the expression of NEAT1. In addition, phenotypic transformation was examined following different treatments in epithelial cells and macrophages. The results suggested that the expression of NEAT1 was high in IBD and was involved in the inflammatory response by regulating the intestinal epithelial barrier and through exosome­mediated polarization of macrophages. The downregulation of NEAT1 suppressed the inflammatory response by modulating the intestinal epithelial barrier and through exosome­mediated polarization of macrophages in IBD. The results of the present study revealed a potential strategy of targeting NEAT1 for IBD therapy.

[Characteristics of Crohn's disease under double balloon enteroscopy].

OBJECTIVE: To observe ulcer characteristics of Crohn's disease under double balloon enteroscopy, and to evaluate the correlation between endoscopic severity and clinical manifestations.
 Methods: A prospective, observational study from July 2015 to December 2016 in the Third Xiangya Hospital, Central South University, we selected 45 patients with positive double-balloon enteroscopy (DBE) and confirmed Crohn's disease. Two digestive internal physician observed the ulcer characteristics of Crohn's disease under double balloon enteroscopy, and gave a simple endoscopic score for CD (SES-CD). We analyzed the correlation between SES-CD and Crohn's disease activity index (CDAI).
 Results: DBE indicated 24 patient ulcers (53.33%) locating at the end of the ileum, 5 (11.11%) locating at ileocolon, 16 (35.56%) locating at upper gatrointestinal tract and they did not affect the end of the ileum. Among them, 8 cases (17.78%) affected only jejunum. Thirty-two patients with longitudinal ulcers in Crohn's disease, accounting for 71.11%. There was no correlation between SES-CD score and CDAI score (r=0.237, P=0.136).
 Conclusion: The ulcerative appearance in Crohn's disease were diverse under double balloon enteroscopy. Crohn's disease could only affect the upper gastrointestinal tract or jejunum. The unwounded ileum and ileocecal valve couldn't be a sign to exclude Crohn's disease. CDAI score couldn't fully assess the prognosis of Crohn's disease.

Assessment of Quality of Life in Chinese Patients With Inflammatory Bowel Disease and their Caregivers.

BACKGROUND: Chronic diseases such as inflammatory bowel disease (IBD) usually affect the psychological status and health-related quality of life (HRQOL) of patients and their caregivers. The aim of this study was to evaluate the level of anxiety, depression, and HRQOL and find the risk factors predictive of HRQOL in IBD patients and their caregivers in a Chinese population. METHODS: One hundred four adult patients with IBD, 102 family caregivers, and 99 healthy controls were enrolled. They completed self-administered surveys related to QOL and psychological questionnaires, including the Short Inflammatory Bowel Disease Questionnaire (patients only), the Short Form-36 Health Survey (SF-36), Self-rating Anxiety Scale (SAS), and Self-rating Depression Scale (SDS). RESULTS: Both the mean SAS total score and the mean SDS total score among the patients and the caregivers were found to be significantly higher than those among the general population (P < 0.05). Total SF-36 score was significantly different between the patients and the general population (P = 0.001), and between caregivers and the general population (P = 0.011). The result showed that the total SF-36 score of the patients had a significant negative correlation with SAS score in the patients (P = 0.040), SDS score in the patients (P = 0.004), annual income (P = 0.036), use of biologicals (P = 0.028), frequency of hospitalization in the last year (P = 0.033), and severity of IBD (P = 0.021). The total SF-36 score of the caregivers was significantly and negatively correlated with SDS score in the caregivers (P = 0.010), SDS score in the patients (P = 0.010), use of biologicals (P = 0.013), and frequency of hospitalization in the last year (P = 0.010) of the patients. CONCLUSIONS: A large proportion of IBD patients and their caregivers experience a high level of anxiety and depression and an impaired HRQOL. Higher levels of anxiety and depression, annual income, use of biologicals, higher frequency of hospitalization in the last year, and disease activity were independent predictors of reduced patient HRQOL; higher levels of depression in both caregivers and patients, use of biologicals, and frequency of hospitalization in the last year of the patients were independent predictors of reduced caregiver HRQOL.

Cronkhite-Canada syndrome: A case report.

Cronkhite-Canada syndrome (CCS) is a rare non-inherited condition characterized by gastrointestinal (GI) hamartomatous polyposis, alopecia, onychodystrophy, hyperpigmentation, weight loss and diarrhea. The etiology is most likely autoimmune and diagnosis is based on patient history, physical examination, endoscopic findings of GI polyposis and histology. The disease is very rare; thus far more than 500 cases of CCS have been reported globally. A 58-years-old male with CCS was reported in the present case study. The patient experienced a history of diarrhea and hematochezia for 4 months, with abdominal pain for 1 month and additional nail and toenail loss for half a month. The clinical, endoscopic and histological data confirmed the diagnosis.

Evaluation of 22G fine-needle aspiration (FNA) versus fine-needle biopsy (FNB) for endoscopic ultrasound-guided sampling of pancreatic lesions: a prospective comparison study.

BACKGROUND: To compare the diagnostic yield and safety of 22G endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) and endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) in the diagnosis of pancreatic solid lesions. METHODS: Between April 2014 and September 2015, 36 patients with pancreatic solid lesions were included for endoscopic ultrasound test. Patients were randomly divided into two groups: EUS-FNA (n = 18) and EUS-FNB (n = 18). Each nidus was punctured three times (15 ~ 20 insertions for each puncture) with a 22G needle. The core specimens were analyzed, and the diagnostic yields of FNA and FNB were evaluated. RESULTS: The procedure success rate was 100% with no complications. Cytological and histological examinations found that the diagnostic yield of FNB and FNA were both 83.3%. To get a definitive diagnosis, FNB needed fewer punctures than FNA (1.11 vs. 1.83; P  <  0.05). CONCLUSIONS: 22G EUS-FNB is a safe and effective way to diagnose pancreatic solid lesions. FNB required a lower number of needle passes to achieve a diagnosis compared with FNA.

MicroRNA-34a suppresses colorectal cancer metastasis by regulating Notch signaling.

Dysregulation of microRNA (miRNA/miR) expression is causally associated with cancer initiation and progression. However, the precise mechanisms by which dysregulated miRNAs induce colorectal tumorigenesis remain unknown. In the present study, downregulation of miR-34a was identified in colorectal cancer cell lines and clinical specimens. Clinical studies revealed that miR-34a expression was negatively associated with distant metastasis, and positively associated with differentiation and survival of human colorectal cancer specimens. In vitro miRNA functional assays demonstrated that miR-34a bound to the putative 3'-untranslated regions of Notch1 and Jagged1 in SW480 cells, and thereby attenuated the migration and invasion of the colon cancer cells. It was additionally identified that miR-34a downregulated the expression of vimentin and fibronectin via Notch1 and Jagged1. Overall, these data indicate that miR-34a serves a key role in suppressing colorectal cancer metastasis by targeting and regulating Notch signaling.

Incomplete ileus and hemafecia as the presenting features of multi-organ involved primary systemic AL amyloidosis: a rare case report.

BACKGROUND: AL Amyloidosis is known to be a systemic disease affecting multiple organs and tissue while it's rare that patients present with gastrointestinal symptoms at first and later develop multiple-organ dysfuction. Clinical signs are not specific and the diagnosis is rarely given before performing immunofixation and endoscopy with multiple biopsies. We would like to emphasize the value of precise diagnostic process of AL amyloidosis. CASE PRESENTATION: In this case report, we describe a 56-year-old man who presented with recurrent periumbilical pain for 4 months and gradually worsened over a month. After a series of tests, he was finally diagnosed with primary systemic AL amyloidosis. He was treated with a chemotherapy regimen (Melphalan, dexamethasone and thalidomide) achieving a good clinical response. CONCLUSION: On account of the high misdiagnosis rate, establishing the most precise diagnosis in first time with typing amyloidogenic protein becomes increasingly vital. Although the presenting feature is usually nonspecific, AL amyloidosis ought to be considered when multiple organs are involved in a short period.

[Identification of the interacting proteins with S100A8 or S100A9 by affinity purification and mass spectrometry].

OBJECTIVE: To identify the interacting proteins with S100A8 or S100A9 in HEK293 cell line by flag-tag affinity purification and liquid chromatography mass spectrometry/mass spectrometry (LC-MS/MS).
 Methods: The p3×Flag-CMV-S100A8 and p3×Flag-CMV-S100A9 expression vectors were constructed by inserting S100A8 or S100A9 coding sequence. The recombinant plasmids were then transfected into HEK293 cells. Affinity purification and LC-MS/MS were applied to identify the proteins interacting with S100A8 or S100A9. Bioinformatics analysis was used to seek the gene ontology of the interacting proteins. Co-immunoprecipitation (Co-IP) was applied to confirm the proteins interacted with S100A8 or S100A9.
 Results: Fourteen proteins including pyruvate kinase, muscle (PKM), nucleophosmin (NPM1) and eukaryotic translation initiation factor 5A (EIF5A), which potentially interacted with S100A8, were successfully identified by Flag-tag affinity purification followed by LC-MS/MS analysis. Six proteins, such as tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein epsilon (14-3-3ε) and PKM, which potentially interacted with S100A9, were successfully identified. Gene ontology analysis of the identified proteins suggested that proteins interacted with S100A8 or S100A9 were involved in several biological pathways, including canonical glycolysis, positive regulation of NF-κB transcription factor activity, negative regulation of apoptotic process, cell-cell adhesion, etc. Co-IP experiment confirmed that PKM2 can interact with both S100A8 and S100A9, and 14-3-3ε can interact with S100A8.
 Conclusion: PKM2 is identified to interact with both S100A8 and S100A9, while 14-3-3ε can interact with S100A9. These results may provide a new clue for the role of S100A8 or S100A9 in the progression of colitis-associated colorectal cancer.

[Therapeutic effect of anti-CXCL1 neutralizing antibody on acute ulcerative colitis in mice].

OBJECTIVE: To evaluate the therapeutic effect of CXCL1 monoclonal antibody on dextra sulfate sodium (DSS)-induced acute ulcerative colitis (UC) in mice, and to elucidate its effect on the expressions of TNF-α, IFN-γ, IL-17 and IL-10 as well as neutrophil infiltration.
 Methods: Female BALB/c mice were randomly divided into a normal group (DSS-), a disease group (DSS+saline), an anti-CXCL1 antibody group (DSS+anti-CXCL1 Ab) and a treatment control group (DSS+IgG Ab). The DSS+saline, DSS+anti-CXCL1 Ab and DSS+anti-CXCL1 Ab groups were given 3.5% DSS solution as drinking water to induce acute intestinal inflammation, while the normal control was given distilled water freely. The DSS+anti-CXCL1 Ab mice were intraperitoneal injected with anti-CXCL1 Ab (4 mg/kg) on the 3rd and 6th day. Same amount of rat IgG Ab was given in the DSS+IgG Ab group. The normal group and the disease group were injected with 0.9% sodium chloride solution. The value of disease activity index (DAI) and the injury of colorectal tissue were measured. The levels of TNF-α, IFN-γ, IL-10 and IL-17 in colonic tissues of mice were detected by RT-PCR. Myeloperoxidase (MPO), a specific marker of neutrophils was measured by immunohistochemistry.
 Results: Compared with the normal control group, DAI score and colorectal injury score in the disease group were significantly increased, but the DAI and colorectal in the mice with acute ulcerative colitis tissue damage score were significantly reduced after anti-CXCL1 Ab intervention. Compared with the normal control group, mRNA levels of TNF-α, IFN-γ and IL-17 in the colorectal tissues were significantly elevated (P<0.05) in the disease group while the IL-10 was decreased; these effects were attenuated by anti-CXCL1 Ab intervention (P<0.05). Immunohistochemistry showed that the infiltration of neutrophils (MPO+) in the colon tissue was significantly increased in the disease group, while the anti-CXCL1 Ab treatment could significantly reduce the neutrophil infiltration in colon tissue (P<0.05).
 Conclusion: Anti-CXCL1 Ab relieves the progression of DSS-induced acute ulcerative colitis by suppressing proinflammatory expression and neutrophil infiltration.

Suppression Colitis and Colitis-Associated Colon Cancer by Anti-S100a9 Antibody in Mice.

The association between chronic inflammation and cancer has long been recognized. The inflammatory bowel disease ulcerative colitis frequently progresses to colon cancer; however, the underlying mechanism is still unclear. S100a9 has been emerged as an important pro-inflammatory mediator in acute and chronic inflammation, and the aberrant expression of S100a9 also contributes to tumorigenic processes such as cell proliferation, angiogenesis, metastasis, and immune evasion. We previously revealed that S100a8 and S100a9 are highly activated and play an important role in the process of colitis-associated carcinogenesis, which suggests an attractive therapeutic target for ulcerative colitis and related colon cancer. Here, we report that administration of a neutralizing anti-S100a9 antibody significantly ameliorated dextran sulfate sodium (DSS)-induced colitis and accompanied by diminished cellular infiltrate of innate immunity cells (macrophages, neutrophils, and dendritic cells) and production of pro-inflammatory cytokines (Tnfα, Il1ß, Ifnγ, Il6, Il17a, Il23a, Il4, and Il12a). The protective effect of anti-S100a9 antibody treatment was also observed in azoxymethane (AOM)/DSS-induced colitis-associated cancer (CAC) mouse model. The inflammatory response, tumor cell proliferation, and immune cells infiltration in the colon tissues were suppressed by anti-S100a9 antibody. Gene expression profiling showed that key pathways known to be involved in CAC development, such as Wnt signaling pathway, PI3K-Akt signaling pathway, cytokine-cytokine receptor interaction, and ECM-receptor interaction pathway, were suppressed after treatment with anti-S100a9 antibody in CAC mice. In view of the protective effect of neutralizing anti-S100a9 antibody against DSS-induced colitis and AOM/DSS-induced CAC in mouse model, this study suggests that anti-S100a9 antibody may provide a novel therapeutic approach to treat ulcerative colitis and may decrease the risk for developing CAC.

[Experience in transumbilical endoscopic surgery diagnosis for 3 cases of pseudomyxoma peritonei].

Three patients of pseudomyxoma peritonei who were diagnozed by transumbilical endoscopic surgery (TUES) were reviewed retrospectively from September 2014 to November 2014. Three cases of ascites patients underwent TUES were diagnozed as pseudomyxoma peritonei. All operations were successful. No open surgery or laparoscopic surgery was required. The mean operative time was (45±16) min; the mean intraoperative blood loss was 510 mL; the mean hospital stay time was 3 days. During the follow up of 911 months, no obvious scar was observed. Cosmetic results appear to be excellent. All patients were treated with intraperitoneal hyperthermia and chemotherapy. The survival rate was 100%. As a novel scarless endoscopic invasive abdominal surgery, TUES has high clinical value with the advantages such as small trauma, no scars, small risk and low cost in the diagnosis of unexplained ascites.

[Association between serum levels of S100A8/S100A9 and clinical features of colorectal cancer patients].

OBJECTIVE: To analyze the association between serum levels of S100A8/S100A9 and clinicopathological features of colorectal cancer patients.
 METHODS: A total of 82 patients with CRC and 14 healthy controls were enrolled for this study. The levels of S100A8 and S100A9 in serum were detected by ELISA assay. The association between S100A8/S100A9 and clinicopathological features was analyzed by student-t test and one-way ANOVA. Receiver Operating Characteristic curve was used to analyze diagnostic efficiency of serum S100A8 and S100A9 for colon rectal cancer. Logistic regression model was also established to analyze the possible risk factors for elevation of S100A8/S100A9.
 RESULTS: The levels of S100A8 and S100A9 were (1 403.3±593.7) and (2 890.3±994.9) pg/mL in patients with colon cancer, and (712.8±265.3) and (1 492.7±564.6) pg/mL in controls, respectively, with significant difference between the two groups (P<0.01). The similar results were found in rectal cancer patients, with a level of S100A8 and S100A9 at (1 417.7±666.5) and (3 026.7±887.6) pg/mL, respectively. Diagnostic sensitivity and specificity of S100A8 and S100A9 are better than traditional biomarkers. The levels of S100A9 in serum of CRC patients were correlated with clinical stages and distant metastasis. Serum levels of S100A9 in patients of stage III [(3 111.9±178.5) pg/mL] and stage IV [(3 831.4±278.5) pg/mL] were significantly (P<0.01) higher than that in stage I [(2 276.1±167.4) pg/mL], whereas there was significant change in S100A8 levels. Logistic regression showed the possible risk factors for the elevation of S100A9, including depth of invasion, lymphatic metastasis and degree of differentiation (P<0.05).
 CONCLUSION: Serum level of S100A8 and S100A9 in CRC patients were significantly increased and serum level of S100A9 was positively correlated with the malignant features of CRC.

The tumor suppressor miR-138-5p targets PD-L1 in colorectal cancer.

microRNAs (miRNAs) play critical roles in cancer development and progression. This study investigated the effects of miR-138-5p in human colorectal cancer (CRC) development. miR-138-5p was frequently downregulated in CRC tissues and was associated with advanced clinical stage, lymph node metastasis and poor overall survival. We found that miR-138-5p decreased expression of programmed cell death ligand 1 (PD-L1) through interaction with its PD-L1 3' untranslated region. miR-138-5p also dramatically suppressed CRC cell growth in vitro and inhibited tumorigenesis in vivo. PD-L1 and miR-138-5p levels were inversely correlated in human CRC tumors, and miR-138-5p inhibited PD-L1 expression in tumor models. These results suggest that miR-138-5p is a tumor suppressor in CRC, and its effects are exerted at least partially through PD-L1 downregulation. Low miR-138-5p and high PD-L1 levels correlated with shorter overall CRC patient survival, indicating that miR-138-5p and PD-L1 may serve as CRC biomarkers for risk group assignment, optimal therapy selection and clinical outcome prediction. Targeting PD-L1, possibly by administering miR-138-5p mimics, might be a clinically effective anti-CRC therapeutic strategy.