The Mir181ab1 cluster promotes KRAS-driven oncogenesis and progression in lung and pancreas

Valencia, Karmele; Erice, Oihane; Kostyrko, Kaja; Hausmann, Simone; Guruceaga, Elizabeth; Tathireddy, Anuradha; Flores, Natasha; Sayles, Leanne C.; Lee, Alex G.; Fragoso, Rita; Sun, Tian; Vallejo, Adrián; Román, Marta Cimavilla; Entrialgo‐Cadierno, Rodrigo; Miguéliz, Itziar; Razquin, Nerea; Fortes, Puri; Lecanda, Fernando; Lü, Jun; Ponz-Sarvisé, Mariano; Chen, Chang Zheng; Mazur, Paweł K.; Sweet-Cordero, E. Alejandro; Vicent, Silvestre

doi:10.1172/jci129012

Cited by 33 publications

(22 citation statements)

References 82 publications

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“…Also, a prominent KRAS signature has been linked to the activation of several important transcription factors, including GATA3 29 . Overexpression of GATA3 was seen in KRAS mutant lung cancer cells and further up‐regulated the tumorigenesis through miRNAs 30 …”

Section: Discussionmentioning

confidence: 99%

Clinicopathological and molecular characterisation of papillary renal neoplasm with reverse polarity and its renal papillary adenoma analogue

Chang

Hang

et al. 2021

Histopathology

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Aims Papillary renal neoplasm with reverse polarity (PRNRP) is a newly defined entity with distinct histomorphology and recurrent KRAS mutation. It has been estimated to constitute 4% of previously diagnosed papillary renal cell carcinoma (PRCC). Renal papillary adenoma (PA) is suggested to be the precursor of PRCC. This study aimed to investigate the association between PRNRP and PA, particularly the morphologically similar type D PA. Methods and results Nephrectomy specimens of PRCC and PA from our 10‐year pathology archives were retrieved and reviewed. GATA3 immunohistochemistry and RAS/BRAF testing were performed in all cases reclassified as PRNRP and all PAs with sufficient materials. Overall, PRNRP accounted for 9.1% (10 of 110) of PRCC and there was no recurrence/metastasis with a mean follow‐up period of 39 months. Three novel morphological features were described, including clear cell change, mast cell infiltration and metaplastic ossification. Nine of the 10 PRNRPs showed diffuse and strong GATA3 expression and KRAS missense mutations at codon 12. One case exhibited moderate GATA3 staining on 80% of the tumour cells and RAS/BRAF wild‐type. In a total of 73 PAs, 11 were classified as type D. GATA3 expression was significantly more frequent in type D versus non‐type D PAs (100 versus 35%, P < 0.01). KRAS missense mutations were identified in six of eight (75%) of the type D PAs but none of the 18 non‐type D PAs. Conclusions Type D PA was different from other types of PA and represented an analogue or a small‐sized PRNRP for their identical morphology, immunophenotype and molecular signature.

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Section: Discussionmentioning

confidence: 99%

Clinicopathological and molecular characterisation of papillary renal neoplasm with reverse polarity and its renal papillary adenoma analogue

Chang

Hang

et al. 2021

Histopathology

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“…27 Massive research showed the important effects of miRNAs during the development of multiple cancers. 28,29 In triple-negative breast cancer, miR-551b-3p can activate the OSM signaling pathway, thus inhibiting the occurrence and development of tumors. 30 In CSCC, the expression patterns of mir-205 and mir-203 showed a typical negative correlation, which could be used as prognostic markers.…”

Section: Discussionmentioning

confidence: 99%

<p>microRNA-26a Directly Targeting MMP14 and MMP16 Inhibits the Cancer Cell Proliferation, Migration and Invasion in Cutaneous Squamous Cell Carcinoma</p>

Wang¹,

Li²,

Zhao³

et al. 2020

CMAR

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Purpose: To investigate the specific effect and underlying mechanism of microRNA-26a-5p (miR-26a) in cutaneous squamous cell carcinoma (CSCC). Methods: miR-26a and MMP14/16 mRNA expression were detected by qRT-PCR analysis. Functional experiments were used to detect the role of miR-26a on CSCC progression. Western blot was used for protein detection. Luciferase assay was used to detect miR-26a directly targeting MMP14 and MMP16. Xenograft nude mice model was used to determine the effect of miR-26a on tumorigenesis. Results: miR-26a was decreased in CSCC tissues and cells. Forced miR-26a suppressed the progression of SCL-1 and A431 cells. Furthermore, miR-26a directly targeted MMP14 and MMP16 to inhibit their expression. Forced expression of MMP14 and MMP16 removed the miR-26a's inhibitory effect on CSCC development. The in vivo tumor growth assay showed that miR-26a suppressed CSCC tumorigenesis by targeting MMP14 and MMP16. Conclusion: Our study suggested miR-26a inhibits cancer cell proliferation, migration and invasion in CSCC by targeting MMP14 and MMP16.

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“…Regarding the relevance of miR-181a in PDAC initiation, it was shown that miR-181ab1 cluster tunes this process in Ptf1aCre/+, KrasLSLG12D/+ Trp53fl/fl, and Mir181ab1−/− mice [ 25 ]. Mir181ab1 knock-out developed less PanIN lesions, and it had less aggressive pancreatic tumours than controls.…”

Section: Discussionmentioning

confidence: 99%

MicroRNAs Deregulated in Intraductal Papillary Mucinous Neoplasm Converge on Actin Cytoskeleton-Related Pathways That Are Maintained in Pancreatic Ductal Adenocarcinoma

Fernandez-Castañer

Vila-Casadesús

Vila-Navarro

et al. 2021

Cancers

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Intraductal papillary mucinous neoplasms (IPMN) are pancreatic cystic lesions that can develop into pancreatic ductal adenocarcinoma (PDAC). Although there is an increasing incidence of IPMN diagnosis, the mechanisms of formation and progression into invasive cancer remain unclear. MicroRNAs (miRNAs) are small non-coding RNAs, repressors of mRNA translation, and promising diagnostic biomarkers for IPMN and PDAC. Functional information on the role of early-altered miRNAs in this setting would offer novel strategies for tracking the IPMN-to-PDAC progression. In order to detect mRNAs that are likely to be under miRNA regulation in IPMNs, whole transcriptome and miRNome data from normal pancreatic tissue (n = 3) and IPMN lesions (n = 4) were combined and filtered according to negative correlation and miRNA-target prediction databases by using miRComb R package. Further comparison analysis with PDAC data allowed us to obtain a subset of miRNA-mRNA pairs shared in IPMN and PDAC. Functional enrichment analysis unravelled processes that are mainly related with cell structure, actin cytoskeleton, and metabolism. MiR-181a appeared as a master regulator of these processes. The expression of selected miRNA-mRNA pairs was validated by qRT-PCR in an independent cohort of patients (n = 40), and then analysed in different pancreatic cell lines. Finally, we generated a cellular model of HPDE cells stably overexpressing miR-181a, which showed a significant alteration of actin cytoskeleton structures accompanied by a significant downregulation of EPB41L4B and SEL1L expression. In situ hybridization of miR-181a and immunohistochemistry of EPB41L4B and SEL1L in pancreatic tissues (n = 4 Healthy; n = 3 IPMN; n = 4 PDAC) were also carried out. In this study, we offer insights on the potential implication of miRNA alteration in the regulation of structural and metabolic changes that pancreatic cells experience during IPMN establishment and that are maintained in PDAC.

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The Mir181ab1 cluster promotes KRAS-driven oncogenesis and progression in lung and pancreas

Cited by 33 publications

References 82 publications

Clinicopathological and molecular characterisation of papillary renal neoplasm with reverse polarity and its renal papillary adenoma analogue

Clinicopathological and molecular characterisation of papillary renal neoplasm with reverse polarity and its renal papillary adenoma analogue

<p>microRNA-26a Directly Targeting MMP14 and MMP16 Inhibits the Cancer Cell Proliferation, Migration and Invasion in Cutaneous Squamous Cell Carcinoma</p>

MicroRNAs Deregulated in Intraductal Papillary Mucinous Neoplasm Converge on Actin Cytoskeleton-Related Pathways That Are Maintained in Pancreatic Ductal Adenocarcinoma

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