The Experts below are selected from a list of 89520 Experts worldwide ranked by ideXlab platform
Nancy L. Allbritton - One of the best experts on this subject based on the ideXlab platform.
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decreased colonic activin receptor like kinase 1 disrupts epithelial barrier integrity in patients with crohn s disease
Cellular and molecular gastroenterology and hepatology, 2020Co-Authors: Takahiko Toyonaga, Benjamin P Keith, Jasmine B Barrow, Matthew S Schaner, Elisabeth A Wolber, Caroline Beasley, Jennifer Huling, Yuli Wang, Erin C Steinbach, Nancy L. AllbrittonAbstract:Background & Aims Intestinal epithelial cell (IEC) barrier dysfunction is critical to the development of Crohn’s disease (CD). However, the mechanism is understudied. We recently reported increased microRNA-31-5p (miR-31-5p) expression in colonic IECs of CD patients, but downstream targets and functional consequences are unknown. Methods microRNA-31-5p target genes were identified by integrative analysis of RNA- and small RNA-sequencing data from colonic mucosa and confirmed by quantitative polymerase chain reaction in colonic IECs. Functional characterization of activin receptor-like kinase 1 (ACVRL1 or ALK1) in IECs was performed ex vivo using 2-dimensional cultured human primary colonic IECs. The impact of altered colonic ALK1 signaling in CD for the risk of surgery and endoscopic relapse was evaluated by a multivariate regression analysis and a Kaplan–Meier estimator. Results ALK1 was identified as a target of miR-31-5p in colonic IECs of CD patients and confirmed using a 3’-untranslated region reporter assay. Activation of ALK1 restricted the proliferation of colonic IECs in a 5-ethynyl-2-deoxyuridine proliferation assay and down-regulated the expression of stemness-related genes. Activated ALK1 signaling increased colonic IEC differentiation toward colonocytes. Down-regulated ALK1 signaling was associated with increased stemness and decreased colonocyte-specific marker expression in colonic IECs of CD patients compared with healthy controls. Activation of ALK1 enhanced epithelial barrier integrity in a transepithelial electrical resistance permeability assay. Lower colonic ALK1 expression was identified as an independent risk factor for surgery and was associated with a higher risk of endoscopic relapse in CD patients. Conclusions Decreased colonic ALK1 disrupted colonic IEC barrier integrity and was associated with poor clinical outcomes in CD patients.
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decreased colonic activin receptor like kinase 1 disrupts epithelial barrier integrity and is associated with a poor clinical outcome in crohns disease
bioRxiv, 2020Co-Authors: Takahiko Toyonaga, Benjamin P Keith, Jasmine B Barrow, Matthew S Schaner, Elisabeth A Wolber, Caroline Beasley, Jennifer Huling, Nancy L. Allbritton, Yuli Wang, Nicole ChaumontAbstract:Objective: Intestinal epithelial cell (IEC) barrier dysfunction is critical to the development of Crohns disease (CD). However, the mechanism is understudied. We recently reported increased microRNA-31-5p (miR-31-5p) expression in colonic IECs of CD patients, but downstream targets are unknown. Design: MiR-31-5p target genes were identified by integrative analysis of RNA- and small RNA-sequencing data from colonic mucosa and confirmed by qPCR in colonic IECs. Functional characterization of Activin Receptor-Like Kinase 1 (ACVRL1 or ALK1) in IECs was performed ex vivo using 2 dimensional-cultured human primary colonic IECs. The impact of altered colonic ALK1 signaling in CD for the risk of surgery and endoscopic relapse was evaluated by a multivariate regression analysis and a Kaplan-Meier estimator. Results: ALK1 was identified as a target of miR-31-5p in colonic IECs of CD patients and confirmed using a 3-UTR reporter assay. Activation of ALK1 restricted the proliferation of colonic IECs in an EdU proliferation assay and down-regulated the expression of stemness-related genes. Activated ALK1 signaling directed the fate of colonic IEC differentiation toward colonocytes. Down-regulated ALK1 signaling was associated with increased stemness and decreased colonocyte-specific marker expression in colonic IECs of CD patients compared to healthy controls. Activation of ALK1 enhanced epithelial barrier integrity in a trans-epithelial electrical resistance permeability assay. Lower colonic ALK1 expression was identified as an independent risk factor for surgery and associated with a higher risk of endoscopic relapse in CD patients. Conclusion: Decreased colonic ALK1 disrupted colonic IEC barrier integrity and associated with deteriorated clinical outcomes in CD patients.
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p149 decreased colonic activin receptor like kinase 1 disrupts epithelial barrier integrity and is associated with a poor clinical outcome in crohn s disease
Gastroenterology, 2020Co-Authors: Takahiko Toyonaga, Benjamin P Keith, Jasmine B Barrow, Matthew S Schaner, Elisabeth A Wolber, Caroline Beasley, Jennifer Huling, Nancy L. Allbritton, Yuli Wang, Terrence S FureyAbstract:Objective: Intestinal epithelial cell (IEC) barrier dysfunction is critical to the development of Crohns disease (CD). However, the mechanism is understudied. We recently reported increased microRNA-31-5p (miR-31-5p) expression in colonic IECs of CD patients, but downstream targets are unknown. Design: MiR-31-5p target genes were identified by integrative analysis of RNA- and small RNA-sequencing data from colonic mucosa and confirmed by qPCR in colonic IECs. Functional characterization of Activin Receptor-Like Kinase 1 (ACVRL1 or ALK1) in IECs was performed ex vivo using 2 dimensional-cultured human primary colonic IECs. The impact of altered colonic ALK1 signaling in CD for the risk of surgery and endoscopic relapse was evaluated by a multivariate regression analysis and a Kaplan-Meier estimator. Results: ALK1 was identified as a target of miR-31-5p in colonic IECs of CD patients and confirmed using a 3-UTR reporter assay. Activation of ALK1 restricted the proliferation of colonic IECs in an EdU proliferation assay and down-regulated the expression of stemness-related genes. Activated ALK1 signaling directed the fate of colonic IEC differentiation toward colonocytes. Down-regulated ALK1 signaling was associated with increased stemness and decreased colonocyte-specific marker expression in colonic IECs of CD patients compared to healthy controls. Activation of ALK1 enhanced epithelial barrier integrity in a trans-epithelial electrical resistance permeability assay. Lower colonic ALK1 expression was identified as an independent risk factor for surgery and associated with a higher risk of endoscopic relapse in CD patients. Conclusion: Decreased colonic ALK1 disrupted colonic IEC barrier integrity and associated with deteriorated clinical outcomes in CD patients.
Xueyun Bi - One of the best experts on this subject based on the ideXlab platform.
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microRNA 31 reduces inflammatory signaling and promotes regeneration in colon epithelium and delivery of mimics in microspheres reduces colitis in mice
Gastroenterology, 2019Co-Authors: Yuhua Tian, Jiuzhi Xu, Sujuan Du, Cong Lv, Xiaole Sheng, Ran Zhao, Yongli Song, Wei Wu, Yuan Li, Xueyun BiAbstract:Background & Aims Levels of microRNA 31 (MIR31) are increased in intestinal tissues from patients with inflammatory bowel diseases and colitis-associated neoplasias. We investigated the effects of this microRNA on intestinal inflammation by studying mice with colitis. Methods We obtained colon biopsy samples from 82 patients with ulcerative colitis (UC), 79 patients with Crohn's disease (CD), and 34 healthy individuals (controls) at Shanghai Tenth People's Hospital. MIR31- knockout mice and mice with conditional disruption of Mir31 specifically in the intestinal epithelium (MIR31 conditional knockouts) were given dextran sulfate sodium (DSS) or 2,4,6-trinitrobenzene sulfonic acid (TNBS) to induce colitis. We performed chromatin immunoprecipitation and luciferase assays to study proteins that regulate expression of MIR31, including STAT3 and p65, in LOVO colorectal cancer cells and organoids derived from mouse colon cells. Partially hydrolyzed alpha-lactalbumin was used to generate peptosome nanoparticles, and MIR31 mimics were loaded onto their surface using electrostatic adsorption. Peptosome–MIR31 mimic particles were encapsulated into oxidized konjac glucomannan (OKGM) microspheres, which were administered by enema into the large intestines of mice with DSS-induced colitis. Intestinal tissues were collected and analyzed by histology and immunohistochemistry. Results Levels of MIR31 were increased in inflamed mucosa from patients with CD or UC, and from mice with colitis, compared with controls. STAT3 and nuclear factor-κB activated transcription of MIR31 in colorectal cancer cells and organoids in response to tumor necrosis factor and interleukin (IL)6. MIR31-knockout and conditional-knockout mice developed more severe colitis in response to DSS and TNBS, with increased immune responses, compared with control mice. MIR31 bound to 3ʹ untranslated regions of Il17ra and Il7r messenger RNAs (RNAs) (which encode receptors for the inflammatory cytokines IL17 and IL7) and Il6st mRNA (which encodes GP130, a cytokine signaling protein). These mRNAs and proteins were greater in MIR31-knockout mice with colitis, compared with control mice; MIR31 and MIR31 mimics inhibited their expression. MIR31 also promoted epithelial regeneration by regulating the WNT and Hippo signaling pathways. OKGM peptosome–MIR31 mimic microspheres localized to colonic epithelial cells in mice with colitis; they reduced the inflammatory response, increased body weight and colon length, and promoted epithelial cell proliferation. Conclusions MIR31, increased in colon tissues from patients with CD or UC, reduces the inflammatory response in colon epithelium of mice by preventing expression of inflammatory cytokine receptors (Il7R and Il17RA) and signaling proteins (GP130). MIR31 also regulates the WNT and Hippo signaling pathways to promote epithelial regeneration following injury. OKGM peptosome–MIR31 microspheres localize to the colon epithelium of mice to reduce features of colitis. Transcript Profiling: GSE123556
Takahiko Toyonaga - One of the best experts on this subject based on the ideXlab platform.
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decreased colonic activin receptor like kinase 1 disrupts epithelial barrier integrity in patients with crohn s disease
Cellular and molecular gastroenterology and hepatology, 2020Co-Authors: Takahiko Toyonaga, Benjamin P Keith, Jasmine B Barrow, Matthew S Schaner, Elisabeth A Wolber, Caroline Beasley, Jennifer Huling, Yuli Wang, Erin C Steinbach, Nancy L. AllbrittonAbstract:Background & Aims Intestinal epithelial cell (IEC) barrier dysfunction is critical to the development of Crohn’s disease (CD). However, the mechanism is understudied. We recently reported increased microRNA-31-5p (miR-31-5p) expression in colonic IECs of CD patients, but downstream targets and functional consequences are unknown. Methods microRNA-31-5p target genes were identified by integrative analysis of RNA- and small RNA-sequencing data from colonic mucosa and confirmed by quantitative polymerase chain reaction in colonic IECs. Functional characterization of activin receptor-like kinase 1 (ACVRL1 or ALK1) in IECs was performed ex vivo using 2-dimensional cultured human primary colonic IECs. The impact of altered colonic ALK1 signaling in CD for the risk of surgery and endoscopic relapse was evaluated by a multivariate regression analysis and a Kaplan–Meier estimator. Results ALK1 was identified as a target of miR-31-5p in colonic IECs of CD patients and confirmed using a 3’-untranslated region reporter assay. Activation of ALK1 restricted the proliferation of colonic IECs in a 5-ethynyl-2-deoxyuridine proliferation assay and down-regulated the expression of stemness-related genes. Activated ALK1 signaling increased colonic IEC differentiation toward colonocytes. Down-regulated ALK1 signaling was associated with increased stemness and decreased colonocyte-specific marker expression in colonic IECs of CD patients compared with healthy controls. Activation of ALK1 enhanced epithelial barrier integrity in a transepithelial electrical resistance permeability assay. Lower colonic ALK1 expression was identified as an independent risk factor for surgery and was associated with a higher risk of endoscopic relapse in CD patients. Conclusions Decreased colonic ALK1 disrupted colonic IEC barrier integrity and was associated with poor clinical outcomes in CD patients.
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decreased colonic activin receptor like kinase 1 disrupts epithelial barrier integrity and is associated with a poor clinical outcome in crohns disease
bioRxiv, 2020Co-Authors: Takahiko Toyonaga, Benjamin P Keith, Jasmine B Barrow, Matthew S Schaner, Elisabeth A Wolber, Caroline Beasley, Jennifer Huling, Nancy L. Allbritton, Yuli Wang, Nicole ChaumontAbstract:Objective: Intestinal epithelial cell (IEC) barrier dysfunction is critical to the development of Crohns disease (CD). However, the mechanism is understudied. We recently reported increased microRNA-31-5p (miR-31-5p) expression in colonic IECs of CD patients, but downstream targets are unknown. Design: MiR-31-5p target genes were identified by integrative analysis of RNA- and small RNA-sequencing data from colonic mucosa and confirmed by qPCR in colonic IECs. Functional characterization of Activin Receptor-Like Kinase 1 (ACVRL1 or ALK1) in IECs was performed ex vivo using 2 dimensional-cultured human primary colonic IECs. The impact of altered colonic ALK1 signaling in CD for the risk of surgery and endoscopic relapse was evaluated by a multivariate regression analysis and a Kaplan-Meier estimator. Results: ALK1 was identified as a target of miR-31-5p in colonic IECs of CD patients and confirmed using a 3-UTR reporter assay. Activation of ALK1 restricted the proliferation of colonic IECs in an EdU proliferation assay and down-regulated the expression of stemness-related genes. Activated ALK1 signaling directed the fate of colonic IEC differentiation toward colonocytes. Down-regulated ALK1 signaling was associated with increased stemness and decreased colonocyte-specific marker expression in colonic IECs of CD patients compared to healthy controls. Activation of ALK1 enhanced epithelial barrier integrity in a trans-epithelial electrical resistance permeability assay. Lower colonic ALK1 expression was identified as an independent risk factor for surgery and associated with a higher risk of endoscopic relapse in CD patients. Conclusion: Decreased colonic ALK1 disrupted colonic IEC barrier integrity and associated with deteriorated clinical outcomes in CD patients.
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p149 decreased colonic activin receptor like kinase 1 disrupts epithelial barrier integrity and is associated with a poor clinical outcome in crohn s disease
Gastroenterology, 2020Co-Authors: Takahiko Toyonaga, Benjamin P Keith, Jasmine B Barrow, Matthew S Schaner, Elisabeth A Wolber, Caroline Beasley, Jennifer Huling, Nancy L. Allbritton, Yuli Wang, Terrence S FureyAbstract:Objective: Intestinal epithelial cell (IEC) barrier dysfunction is critical to the development of Crohns disease (CD). However, the mechanism is understudied. We recently reported increased microRNA-31-5p (miR-31-5p) expression in colonic IECs of CD patients, but downstream targets are unknown. Design: MiR-31-5p target genes were identified by integrative analysis of RNA- and small RNA-sequencing data from colonic mucosa and confirmed by qPCR in colonic IECs. Functional characterization of Activin Receptor-Like Kinase 1 (ACVRL1 or ALK1) in IECs was performed ex vivo using 2 dimensional-cultured human primary colonic IECs. The impact of altered colonic ALK1 signaling in CD for the risk of surgery and endoscopic relapse was evaluated by a multivariate regression analysis and a Kaplan-Meier estimator. Results: ALK1 was identified as a target of miR-31-5p in colonic IECs of CD patients and confirmed using a 3-UTR reporter assay. Activation of ALK1 restricted the proliferation of colonic IECs in an EdU proliferation assay and down-regulated the expression of stemness-related genes. Activated ALK1 signaling directed the fate of colonic IEC differentiation toward colonocytes. Down-regulated ALK1 signaling was associated with increased stemness and decreased colonocyte-specific marker expression in colonic IECs of CD patients compared to healthy controls. Activation of ALK1 enhanced epithelial barrier integrity in a trans-epithelial electrical resistance permeability assay. Lower colonic ALK1 expression was identified as an independent risk factor for surgery and associated with a higher risk of endoscopic relapse in CD patients. Conclusion: Decreased colonic ALK1 disrupted colonic IEC barrier integrity and associated with deteriorated clinical outcomes in CD patients.
Ran Zhao - One of the best experts on this subject based on the ideXlab platform.
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microRNA 31 reduces inflammatory signaling and promotes regeneration in colon epithelium and delivery of mimics in microspheres reduces colitis in mice
Gastroenterology, 2019Co-Authors: Yuhua Tian, Jiuzhi Xu, Sujuan Du, Cong Lv, Xiaole Sheng, Ran Zhao, Yongli Song, Wei Wu, Yuan Li, Xueyun BiAbstract:Background & Aims Levels of microRNA 31 (MIR31) are increased in intestinal tissues from patients with inflammatory bowel diseases and colitis-associated neoplasias. We investigated the effects of this microRNA on intestinal inflammation by studying mice with colitis. Methods We obtained colon biopsy samples from 82 patients with ulcerative colitis (UC), 79 patients with Crohn's disease (CD), and 34 healthy individuals (controls) at Shanghai Tenth People's Hospital. MIR31- knockout mice and mice with conditional disruption of Mir31 specifically in the intestinal epithelium (MIR31 conditional knockouts) were given dextran sulfate sodium (DSS) or 2,4,6-trinitrobenzene sulfonic acid (TNBS) to induce colitis. We performed chromatin immunoprecipitation and luciferase assays to study proteins that regulate expression of MIR31, including STAT3 and p65, in LOVO colorectal cancer cells and organoids derived from mouse colon cells. Partially hydrolyzed alpha-lactalbumin was used to generate peptosome nanoparticles, and MIR31 mimics were loaded onto their surface using electrostatic adsorption. Peptosome–MIR31 mimic particles were encapsulated into oxidized konjac glucomannan (OKGM) microspheres, which were administered by enema into the large intestines of mice with DSS-induced colitis. Intestinal tissues were collected and analyzed by histology and immunohistochemistry. Results Levels of MIR31 were increased in inflamed mucosa from patients with CD or UC, and from mice with colitis, compared with controls. STAT3 and nuclear factor-κB activated transcription of MIR31 in colorectal cancer cells and organoids in response to tumor necrosis factor and interleukin (IL)6. MIR31-knockout and conditional-knockout mice developed more severe colitis in response to DSS and TNBS, with increased immune responses, compared with control mice. MIR31 bound to 3ʹ untranslated regions of Il17ra and Il7r messenger RNAs (RNAs) (which encode receptors for the inflammatory cytokines IL17 and IL7) and Il6st mRNA (which encodes GP130, a cytokine signaling protein). These mRNAs and proteins were greater in MIR31-knockout mice with colitis, compared with control mice; MIR31 and MIR31 mimics inhibited their expression. MIR31 also promoted epithelial regeneration by regulating the WNT and Hippo signaling pathways. OKGM peptosome–MIR31 mimic microspheres localized to colonic epithelial cells in mice with colitis; they reduced the inflammatory response, increased body weight and colon length, and promoted epithelial cell proliferation. Conclusions MIR31, increased in colon tissues from patients with CD or UC, reduces the inflammatory response in colon epithelium of mice by preventing expression of inflammatory cytokine receptors (Il7R and Il17RA) and signaling proteins (GP130). MIR31 also regulates the WNT and Hippo signaling pathways to promote epithelial regeneration following injury. OKGM peptosome–MIR31 microspheres localize to the colon epithelium of mice to reduce features of colitis. Transcript Profiling: GSE123556
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microRNA 31 activates the ras pathway and functions as an oncogenic microRNA in human colorectal cancer by repressing ras p21 gtpase activating protein 1 rasa1
Journal of Biological Chemistry, 2013Co-Authors: Feng Yu, Ran Zhao, Xi Chen, Chenyu Zhang, Jiangning Chen, Junfeng ZhangAbstract:microRNAs (miRNAs) are known to play a vital role in colorectal cancer. We found a widespread disruption in miRNA expression during colorectal tumorigenesis using microarray and quantitative RT-PCR analysis; of the 161 miRNAs altered in colorectal cancer compared with normal adjacent tissue samples, miR-31 was the most significantly dysregulated. We identified candidate targets of miR-31 using bioinformatics approaches and validated RAS p21 GTPase activating protein 1 (RASA1) as a direct target. First, we found an inverse correlation between miR-31 and RASA1 protein levels in vivo. Second, in vitro evidence demonstrated that RASA1 expression was significantly decreased by treatment with pre-miR-31-LV, whereas anti-miR-31-LV treatment increased RASA1 protein levels. Third, a luciferase reporter assay confirmed that miR-31 directly recognizes a specific location within the 3′-untranslated region of RASA1 transcripts. Furthermore, the biological consequences of miR-31 targeting RASA1 were examined by the cell proliferation assay in vitro and by the immunodeficient mouse xenograft tumor model in vivo. Taken together, our results demonstrate for the first time that miR-31 plays a significant role in activating the RAS signaling pathway through the inhibition of RASA1 translation, thereby improving colorectal cancer cell growth and stimulating tumorigenesis.
Meir Preis - One of the best experts on this subject based on the ideXlab platform.
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abstract 5698 microRNA 31 acts as an oncomir in lung cancer by repressing specific tumor suppressors
Cancer Research, 2010Co-Authors: Xi Liu, Lorenzo F Sempere, Haoxu Ouyang, Vincent A Memoli, Angeline S Andrew, Yue Luo, Eugene Demidenko, Murray Korc, Wei Shi, Meir PreisAbstract:microRNAs (miRNAs) encode small RNAs that regulate gene expression. The expression profiles of miRNAs have proven useful to improve classification, diagnostic and prognostic information for human cancers. We sought to uncover miRNAs preferentially over-expressed in lung cancers versus adjacent normal lung tissues. We comprehensively interrogated miRNA array expression profiles conducted on lung cancers versus adjacent normal lung tissues isolated from murine transgenic cyclin E models that were engineered. Notably, miR-136, miR-376a and miR-31 were each significantly over-expressed in murine lung cancers as compared to adjacent normal lung tissues. Real-time RT-PCR and in situ hybridization assays independently confirmed these miRNA expression profiles in paired normal-malignant lung tissues from transgenic mice as well as from a well characterized panel of paired human normal-malignant lung tissues. Knock-down of miR-31, but not other highlighted miRNAs, using a synthetic antagonist significantly repressed lung cancer cell growth and in vivo tumorigenicity. Bioinformatically predicted miR-31 target genes were identified and studied. These included two tumor suppressors: large tumor suppressor 2 (LATS2) and PP2A regulatory subunit B alpha isoform (PPP2R2A) that were each substantially increased by miR-31 knock-down and repressed by miR-31 over-expression. Engineered repression of either LATS2 or PPP2R2A significantly antagonized miR-31-mediated growth inhibition. Luciferase binding assays confirmed that miR-31 directly suppressed LATS2 and PPP2R2A through binding to their respective 3′-untranslated regions (UTRs). Interestingly, miR-31 was inversely expressed relative to these identified target genes in both murine and human lung cancers. Clinical relevance was uncovered using miR-31 in situ hybridization and cyclin E immunohistochemistry assays performed on tissue arrays from the population-based New Hampshire Lung Cancer Registry. As expected, cyclin E expression was significantly associated with miR-31 levels. Real-time RT-PCR assays validated LATS2 and PPP2R2A repression in lung cancers versus adjacent normal lung tissues. Thus, these findings implicate miR-31 as an oncogenic miRNA (oncomir) that exerts its effects by repressing specific tumor suppressors. Taken together, miR-31 is proposed as a novel molecular target for lung cancer therapy and chemoprevention. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5698.
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microRNA 31 functions as an oncogenic microRNA in mouse and human lung cancer cells by repressing specific tumor suppressors
Journal of Clinical Investigation, 2010Co-Authors: Xi Liu, Lorenzo F Sempere, Haoxu Ouyang, Vincent A Memoli, Angeline S Andrew, Yue Luo, Eugene Demidenko, Murray Korc, Wei Shi, Meir PreisAbstract:microRNAs (miRNAs) regulate gene expression. It has been suggested that obtaining miRNA expression profiles can improve classification, diagnostic, and prognostic information in oncology. Here, we sought to comprehensively identify the miRNAs that are overexpressed in lung cancer by conducting miRNA microarray expression profiling on normal lung versus adjacent lung cancers from transgenic mice. We found that miR-136, miR-376a, and miR-31 were each prominently overexpressed in murine lung cancers. Real-time RT-PCR and in situ hybridization (ISH) assays confirmed these miRNA expression profiles in paired normal-malignant lung tissues from mice and humans. Engineered knockdown of miR-31, but not other highlighted miRNAs, substantially repressed lung cancer cell growth and tumorigenicity in a dose-dependent manner. Using a bioinformatics approach, we identified miR-31 target mRNAs and independently confirmed them as direct targets in human and mouse lung cancer cell lines. These targets included the tumor-suppressive genes large tumor suppressor 2 (LATS2) and PP2A regulatory subunit B alpha isoform (PPP2R2A), and expression of each was augmented by miR-31 knockdown. Their engineered repression antagonized miR-31-mediated growth inhibition. Notably, miR-31 and these target mRNAs were inversely expressed in mouse and human lung cancers, underscoring their biologic relevance. The clinical relevance of miR-31 expression was further independently and comprehensively validated using an array containing normal and malignant human lung tissues. Together, these findings revealed that miR-31 acts as an oncogenic miRNA (oncomir) in lung cancer by targeting specific tumor suppressors for repression.