MicroRNA-31 initiates lung tumorigenesis and promotes mutant KRAS-driven lung cancer

Edmonds, Mick D.; Boyd, Kelli L.; Moyo, Tamara K.; Mitra, Ramkrishna; Duszynski, Robert J.; Arrate, Maria Pia; Chen, Xi; Zhao, Zhongming; Blackwell, Timothy S.; Andl, Thomas; Eischen, Christine M.

doi:10.1172/jci82720

Cited by 93 publications

(88 citation statements)

References 52 publications

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“…miR‐31‐5p downregulation in breast cancer is related to tumor metastases, whereas elevated miR‐31‐5p expression in colorectal cancer may be associated with late stage tumors . miR‐31‐5p dysregulation endorses KRAS mutation‐driven NSCLC, and hence plays a key role in lung tumorigenesis . Our current observations that the elevated expression levels of the three miRNAs in sputum and plasma of NSCLC patients further support their important roles in lung carcinogenesis.…”

Section: Discussionsupporting

confidence: 63%

MicroRNA‐based biomarkers for diagnosis of non‐small cell lung cancer (NSCLC)

et al. 2020

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Background The development of biomarkers for the early detection of non‐small cell lung cancer (NSCLC) is clinically important. We have developed miRNA biomarkers in sputum and plasma, respectively, for NSCLC. Herein, we evaluate whether integrated analysis of the miRNAs across the different types of specimens could improve the early detection of NSCLC. Methods Using reverse transcription PCR, we determined expressions of two miRNAs (miRs‐31‐5p and 210‐3p) in sputum and three miRNAs (miRs‐21‐5p, 210‐3p, and 486‐5p) in plasma of a training cohort of 76 NSCLC patients and 72 cancer‐free smokers. The results were validated in a testing cohort of 56 NSCLC patients and 55 cancer‐free smokers. Results The panels of two sputum miRNAs and three plasma miRNAs had 65.8–75.0% sensitivities and 83.3–87.5% specificities for diagnosis of NSCLC in the training cohort. The individual sputum or plasma miRNA panel had a higher sensitivity for squamous cell carcinoma or adenocarcinoma of the lung, respectively. From the miRNAs, we optimized an integrated panel of biomarkers consisting of two sputum miRNAs (miRs‐31‐5p and 210‐3p) and one plasma miRNA (miR‐21‐5p) that had higher sensitivity (85.5%) and specificity (91.7%) for diagnosis of NSCLC compared with the individual panels alone. Furthermore, the performance of the integrated panel of biomarkers was independent of histology and stage of NSCLC, and patients' age, sex, and ethnicity. The performance of the integrated panel of biomarkers was confirmed in the testing cohort. Conclusions Integrating biomarkers across different body fluids would synergistically improve the early detection of NSCLC. Key points Lung cancer is a heterogeneous disease and develops from complex aberrations. Integrating sputum and plasma miRNAs has higher accuracy than when they are used alone

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Section: Discussionsupporting

confidence: 63%

MicroRNA‐based biomarkers for diagnosis of non‐small cell lung cancer (NSCLC)

et al. 2020

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“…Moreover, miR‐122, miR‐27a, and miR‐330‐5p target Sprouty2, leading to enhanced cell proliferation . MicroRNA‐31 targets several negative regulators of the Ras/Raf/ERK pathway, including Sprouty1/3/4 and Spred1/2 . The stability of Sprouty2 protein is regulated by several E3 ubiquitin‐protein ligases, such as c‐Cbl, Siah2, Nedd4‐1, and pVHL, although it is unknown how the stability of other Sprouty proteins is regulated.…”

Section: Regulation Of Sprouty/spred Expressionmentioning

confidence: 99%

The Sprouty/Spred family as tumor suppressors: Coming of age

Kawazoe

Taniguchi

2019

Cancer Science

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The Ras/Raf/ERK pathway is one of the most frequently dysregulated signaling pathways in various cancers. In some such cancers, Ras and Raf are hotspots for mutations, which cause continuous activation of this pathway. However, in some other cancers, it is known that negative regulators of the Ras/Raf/ERK pathway are responsible for uncontrolled activation. The Sprouty/Spred family is broadly recognized as important negative regulators of the Ras/Raf/ERK pathway, and its expression is downregulated in many malignancies, leading to hyperactivation of the Ras/Raf/ERK pathway. After the discovery of this family, intensive research investigated the mechanism by which it suppresses the Ras/Raf/ERK pathway and its roles in developmental and pathophysiological processes. In this review, we discuss the complicated roles of the Sprouty/Spred family in tumor initiation, promotion, and progression and its future therapeutic potential.

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“…miR‐31 plays an important role in different types of cancers, including breast (Sossey‐Alaoui et al, ; Lu et al, ; Körner et al, ; Mulrane et al, ; Viré et al, ), ovarian (Anderson et al, ; Yu et al, ; Hassan et al, ), lung (Liu et al, ; Meng et al, ; Dong et al, ; Edmonds et al, ; Yu et al, ), colon (Cottonham et al, ; Cekaite et al, ; Xu et al, ; Kim et al, ; Li et al, ; Kurihara et al, ), and melanoma (Greenberg et al, ; Asangani et al, ). Intriguingly, even though the expression of miR‐31 is consistently altered in various cancers, miR‐31 can perform either tumor‐suppressive or oncogenic functions, depending on the type of cancer (Table ) (reviewed in Laurila and Kallioniemi, ).…”

Section: Role Of Mir‐31 In Cancer Is Context‐dependentmentioning

confidence: 99%

Function and regulation of microRNA‐31 in development and disease

Stepicheva

Song

2016

Molecular Reproduction Devel

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SUMMARY MicroRNAs (miRNAs) are small noncoding RNAs that orchestrate numerous cellular processes both under normal physiological conditions as well as in diseases. This review summarizes the functional roles and transcriptional regulation of the highly evolutionarily conserved miRNA, microRNA-31 (miR-31). miR-31 is an important regulator of embryonic implantation, development, bone and muscle homeostasis, and immune system function. Its own regulation is disrupted during the onset and progression of cancer and autoimmune disorders such as psoriasis and systemic lupus erythematosus. Limited studies suggest that miR-31 is transcriptionally regulated by epigenetics, such as methylation and acetylation, as well as by a number of transcription factors. Overall, miR-31 regulates diverse cellular and developmental processes by targeting genes involved in cell proliferation, apoptosis, cell differentiation, and cell motility.

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MicroRNA-31 initiates lung tumorigenesis and promotes mutant KRAS-driven lung cancer

Cited by 93 publications

References 52 publications

MicroRNA‐based biomarkers for diagnosis of non‐small cell lung cancer (NSCLC)

MicroRNA‐based biomarkers for diagnosis of non‐small cell lung cancer (NSCLC)

The Sprouty/Spred family as tumor suppressors: Coming of age

Function and regulation of microRNA‐31 in development and disease

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