Regulatory network of miRNA on its target: coordination between transcriptional and post-transcriptional regulation of gene expression

Pu, Mengfan; Chen, Jing; Tao, Zhouteng; Miao, Lijing; Qi, Xinming; Wang, Yizheng; Ren, Jin

doi:10.1007/s00018-018-2940-7

Cited by 356 publications

(255 citation statements)

References 82 publications

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“…Several reports have shown that mRNA and protein is not always strictly linear, but has a more intrinsic and complex dependence. Different regulatory mechanisms (such as synthesis and degradation rates) may play roles in both the synthesized mRNA and the synthesized protein [46][47][48]. In this study, our data showed that IL-17 expression had a positive correlation with the expression of FAS and FASL (r = 0.820, P < 0.01).…”

Section: Associations Between Il-17 Protein Expression and Recurrencesupporting

confidence: 48%

IL-17 affects progression, metastasis, and recurrence of laryngeal cancer via the inhibition of apoptosis through activation of the PI3K/AKT/FAS/FASL pathways

Song

Yang

Zhang

et al. 2019

Preprint

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Background. Cytokines play important roles in development and prognosis of laryngeal cancer (LC). Interleukin-17 (IL-17) from a distinct subset of CD4 + T-cells may significantly induce cancer-elicited inflammation to prevent cancer cells from immune surveillance. Methods. The expression levels of IL-17 were examined among 60 patients with LC. Immunofluorescence co-localization experiments were performed to verify the localization of IL-17 and FAS/FASL in Hep-2 and Tu212 cells. IL-17 was silenced for expression in LC cell lines by siRNA techniques for determination of the role of IL-17 in LC. Results. In our LC patients, cytokines were dysregulated in LC tissues compared with normal tissues. We found that IL-17 was overexpressed in a cohort of 60 LC tumors paired with non-tumor tissues. Moreover, high IL-17 expression was significantly associated with advanced T category, late clinical stage, differentiation, lymph node metastasis, and disease recurrence. In addition, the time-course expression of FAS and FASL was observed after stimulation and treatment with IL-17 stimulator. Finally, in vitro experiments demonstrated that IL-17 functioned as an oncogene by inhibiting the apoptosis of LC cells via the PI3K/AKT/FAS/FASL pathways. Conclusions. Taken together, our findings for the first time demonstrate the role of IL-17 as a tumor promoter and a pro-metastatic factor in LC, indicating that IL-17 may have an oncogenic role and serve as a potential prognostic biomarker and therapeutic target in LC.

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Section: Associations Between Il-17 Protein Expression and Recurrencesupporting

confidence: 48%

IL-17 affects progression, metastasis, and recurrence of laryngeal cancer via the inhibition of apoptosis through activation of the PI3K/AKT/FAS/FASL pathways

Song

Yang

Zhang

et al. 2019

Preprint

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“…Copious reports reveal that miRNAs are widely involved in various cancerous biological behaviors and pathological processes, including GC [10][11][12]. By completely or incompletely base-pairing with the 3 untranslated region (3 UTR) of target messenger RNA (mRNA), miRNA triggers either mRNA degradation or translational repression [13][14][15]. Compelling evidence has indicated that miRNA is emerging as an indispensable modulator of cellular process, including cell proliferation, migration, apoptosis, differentiation, angiogenesis and immune response in various human diseases, especially human cancers…”

Section: Introductionmentioning

confidence: 99%

MiR-876-5p regulates gastric cancer cell proliferation, apoptosis and migration through targeting WNT5A and MITF

Qing-hong

et al. 2019

Bioscience Reports

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MicroRNAs (miRNAs) are reported to play critical roles in various cancers. Recently, mounting miRNAs are found to exert oncogenic or tumor inhibitory role in gastric cancer (GC), however, their potential molecular mechanism in GC remains ill-defined. Currently, we aimed to elucidate the functional and mechanistic impacts of a novel miRNA on GC cellular process. The significant down-regulation of miR-876-5p in GC cells attracted our attention. In function, we performed gain-of-function assays and found that miR-876-5p overexpression repressed proliferative, anti-apoptotic and migratory abilities and epithelial–mesenchymal transition (EMT) of GC cells. By applying bioinformatics prediction and mechanism experiments, we verified that miR-876-5p could double-bind to the 3′ untranslated regions (3′UTRs) of Wnt family member 5A (WNT5A) and melanogenesis associated transcription factor (MITF), thus regulating their mRNA and protein levels. Both WNT5A and MITF were highly expressed in GC cells. Additionally, we conducted loss-of-function assays and confirmed the oncogenic roles of WNT5A and MITF in GC. Finally, rescue assay uncovered a fact that miR-876-5p suppressed GC cell viability and migration, but induced cell apoptosis via targeting WNT5A and MITF. Taken together, we might offer a valuable evidence for miR-876-5p role in GC development.

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“…We identi ed a novel circRNA hsa_circ_0001860 that was downregulated in tissue samples from MPA- CircRNA can participate in biological functions in a variety of ways, and the most common way is acting as miRNA 'sponges' and regulate the expression and activity of the target genes 22 . In our study, we revealed that hsa_circ_0001860 acted as a miRNA sponge for miR-520 h. It is known that miRNAs participate in a majority of biological processes via regulating target gene expression 35 . MiR-520 h has also been studied in various cancers.…”

Section: Discussionmentioning

confidence: 68%

Hsa-circ-0001860 promotes Smad7 to enhance MPA resistance in endometrial cancer via miR-520h

Yuan

Zheng

Zeng

et al. 2020

Preprint

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Background Medroxyprogesterone acetate (MPA) is one of the most commonly prescribed progestin for the treatment of endometrial cancer (EC). Despite initial benefits, many patients ultimately develop progesterone resistance. Circular RNA (circRNA) is a kind of noncoding RNA, contributing greatly to the development of human tumor. However, the role of circular RNA in MPA resistance is unknown. Methods We explored the expression profile of circRNAs in Ishikawa cells treated with (ISK/MPA) or without MPA (ISK) by RNA sequencing, and identified a key circRNA hsa_circ_0001860. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to verify its expression in MPA-resistant cell lines and tissues. CCK8, Transwell and flow cytometry were used to evaluate the functional roles of hsa_circ_0001860 in MPA resistance. The interaction between hsa_circ_0001860 and miR-520h was confirmed by bioinformatics analysis and luciferase reporter assay. Results The expression of hsa_circ_0001860 was significantly downregulated in MPA-resistant cell lines and tissues, and negatively correlated with lymph node metastasis and histological grade of EC. Functional analysis showed that hsa_circ_0001860 knockdown by shRNA promoted the proliferation, migration and invasion and inhibited the apoptosis of Ishikawa cells treated with MPA. Mechanistically, hsa_circ_0001860 promoted Smad7 expression by sponging miR-520h. Conclusion Hsa_circ_0001860 plays an important role in the development of MPA resistance in EC through miR-520h / Smad7 axis, and it could be targeted to reverse the MPA resistance in endometrial cancer.

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Regulatory network of miRNA on its target: coordination between transcriptional and post-transcriptional regulation of gene expression

Cited by 356 publications

References 82 publications

IL-17 affects progression, metastasis, and recurrence of laryngeal cancer via the inhibition of apoptosis through activation of the PI3K/AKT/FAS/FASL pathways

IL-17 affects progression, metastasis, and recurrence of laryngeal cancer via the inhibition of apoptosis through activation of the PI3K/AKT/FAS/FASL pathways

MiR-876-5p regulates gastric cancer cell proliferation, apoptosis and migration through targeting WNT5A and MITF

Hsa-circ-0001860 promotes Smad7 to enhance MPA resistance in endometrial cancer via miR-520h

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