The Molecular Pathogenesis of Tumor-Suppressive miR-486-5p and miR-486-3p Target Genes: GINS4 Facilitates Aggressiveness in Lung Adenocarcinoma

Tomioka, Yuya; Shioiri, Takayuki; Seki, Naohiko; Tanigawa, Kengo; Hagihara, Yoko; Shinmura, Masahiro; Asai, Shunichi; Kikkawa, Naoko; Inoue, Hiromasa; Mizuno, Keiko

doi:10.3390/cells12141885

Cited by 4 publications

(9 citation statements)

References 59 publications

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“…However, LAC and PCT are susceptible to other factors and need dynamic monitoring to predict the prognosis of patients with SCAP. Previously, miR-486-5p has been reported to participate in the development of lung adenocarcinoma and pulmonary arterial hypertension [38][39][40]. Additionally, miR-486-5p was found to link idiopathic pulmonary fibrosis and COVID-19 predicting the development of fibrosis in post-COVID-19 patients [12,13].…”

Section: Discussionmentioning

confidence: 97%

miR-486-5p predicted adverse outcomes of SCAP and regulated K. pneumonia infection via FOXO1

Jin,

Liu,

Cao

et al. 2024

BMC Immunol

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Purpose Severe community-acquired pneumonia (SCAP) is a common respiratory system disease with rapid development and high mortality. Exploring effective biomarkers for early detection and development prediction of SCAP is of urgent need. The function of miR-486-5p in SCAP diagnosis and prognosis was evaluated to identify a promising biomarker for SCAP. Patients and methods The serum miR-486-5p in 83 patients with SCAP, 52 healthy individuals, and 68 patients with mild CAP (MCAP) patients were analyzed by PCR. ROC analysis estimated miR-486-5p in screening SCAP, and the Kaplan-Meier and Cox regression analyses evaluated the predictive value of miR-486-5p. The risk factors for MCAP patients developing SCAP were assessed by logistic analysis. The alveolar epithelial cell was treated with Klebsiella pneumonia to mimic the occurrence of SCAP. The targeting mechanism underlying miR-486-5p was evaluated by luciferase reporter assay. Results Upregulated serum miR-486-5p screened SCAP from healthy individuals and MCAP patients with high sensitivity and specificity. Increasing serum miR-486-5p predicted the poor outcomes of SCAP and served as a risk factor for MCAP developing into SCAP. K. pneumonia induced suppressed proliferation, significant inflammation and oxidative stress in alveolar epithelial cells, and silencing miR-486-5p attenuated it. miR-486-5p negatively regulated FOXO1, and the knockdown of FOXO1 reversed the effect of miR-486-5p in K. pneumonia-treated alveolar epithelial cells. Conclusion miR-486-5p acted as a biomarker for the screening and monitoring of SCAP and predicting the malignancy of MCAP. Silencing miR-486-5p alleviated inflammation and oxidative stress induced by K. pneumonia via negatively modulating FOXO1.

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Section: Discussionmentioning

confidence: 97%

miR-486-5p predicted adverse outcomes of SCAP and regulated K. pneumonia infection via FOXO1

Jin,

Liu,

Cao

et al. 2024

BMC Immunol

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“…We recently created a miRNA expression signature based on LUAD clinical specimens using RNA sequencing [10]. Using this signature, we selected miRNAs with suppressed expression in LUAD tissues.…”

Section: Mirna Expression and Clinical Significance In Patients With ...mentioning

confidence: 99%

“…Small RNAs (miRNAs and siRNAs) were transfected into LUAD cell lines, and cell proliferation, migration, and invasion were evaluated and compared with those of control cells. The transfection procedures of miRNAs and siRNAs were described in our previous studies [10,[15][16][17]. All miRNA precursors were transfected at 10 nM, and all siRNAs were transfected at 5 nM into A549 and H1299 cell lines using RNAiMAX (Invitrogen, Carlsbad, CA, USA).…”

Section: Functional Assay Of Mirnas and Mirna Target Genes In Luad Cellsmentioning

confidence: 99%

“…Traditionally, it was thought that only the guide strand of miRNAs derived from pre-miRNAs was functional in cells, and therefore, cancer research has been focused on the guide strands. Our recent studies revealed that the passenger strand of miRNAs derived from pre-miRNAs is intricately involved in the molecular pathogenesis of human cancers, including lung cancer [9,10]. We can uncover new molecular pathways in cancer cells by examining the molecules regulated by both strands of miRNAs derived from pre-miRNAs.…”

Section: Introductionmentioning

confidence: 99%

“…Recently, we created a miRNA expression signature based on LUAD tissues using RNA sequencing [10]. Analysis of this signature showed that both the guide and passenger strands of pre-miR-139 (miR-139-5p and miR-139-3p, respectively) were downregulated in LUAD tissues.…”

Section: Introductionmentioning

confidence: 99%

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Identification of Tumor-Suppressive miR-139-3p-Regulated Genes: TRIP13 as a Therapeutic Target in Lung Adenocarcinoma

Hagihara,

Tomioka,

Suetsugu

et al. 2023

Cancers

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Analyses of our microRNA (miRNA) expression signature combined with The Cancer Genome Atlas (TCGA) data revealed that both strands of pre-miR-139 (miR-139-5p, the guide strand, and miR-139-3p, the passenger strand) are significantly downregulated in lung adenocarcinoma (LUAD) clinical specimens. Functional analyses of LUAD cells ectopically expressing miR-139-3p showed significant suppression of their aggressiveness (e.g., cancer cell proliferation, migration, and invasion). The involvement of the passenger strand, miR-139-3p, in LUAD pathogenesis, is an interesting finding contributing to the elucidation of unknown molecular networks in LUAD. Of 1108 genes identified as miR-139-3p targets in LUAD cells, 21 were significantly upregulated in LUAD tissues according to TCGA analysis, and their high expression negatively affected the prognosis of LUAD patients. We focused on thyroid hormone receptor interactor 13 (TRIP13) and investigated its cancer-promoting functions in LUAD cells. Luciferase assays showed that miR-139-3p directly regulated TRIP13. siRNA-mediated TRIP13 knockdown and TRIP13 inhibition by a specific inhibitor (DCZ0415) attenuated the malignant transformation of LUAD cells. Interestingly, when used in combination with anticancer drugs (cisplatin and carboplatin), DCZ0415 exerted synergistic effects on cell proliferation suppression. Identifying the molecular pathways regulated by tumor-suppressive miRNAs (including passenger strands) may aid in the discovery of diagnostic markers and therapeutic targets for LUAD.

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Metapath-aggregated multilevel graph embedding for miRNA‒disease association prediction

Cao,

Chen,

Yang

et al. 2023

2023 IEEE International Conference on Bioinformatics and Biomedicine (BIBM)

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The Molecular Pathogenesis of Tumor-Suppressive miR-486-5p and miR-486-3p Target Genes: GINS4 Facilitates Aggressiveness in Lung Adenocarcinoma

Cited by 4 publications

References 59 publications

miR-486-5p predicted adverse outcomes of SCAP and regulated K. pneumonia infection via FOXO1

miR-486-5p predicted adverse outcomes of SCAP and regulated K. pneumonia infection via FOXO1

Identification of Tumor-Suppressive miR-139-3p-Regulated Genes: TRIP13 as a Therapeutic Target in Lung Adenocarcinoma

Metapath-aggregated multilevel graph embedding for miRNA‒disease association prediction

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