ncRNA therapy with miRNA-22-3p suppresses the growth of triple-negative breast cancer

Görür, Ayşegül; Bayraktar, Recep; Ivan, Cristina; Mokhlis, Hamada A.; Bayraktar, Emine; Kahraman, Nermin; Karakaş, Didem; Karamil, Selda; Kabil, Nashwa; Kanlikilicer, Pınar; Aslan, Burcu; Tamer, Lülüfer; Wang, Zhihui; Cristini, Vittorio; López-Berestein, Gabriel; Calin, George A.; Özpolat, Bülent

doi:10.1016/j.omtn.2021.01.016

Cited by 36 publications

(27 citation statements)

References 23 publications

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“…miR-22 is downregulation in TNBC, is associated with migration and metastasis. miR-22 exerts its effect through eukaryotic elongation factor 2 kinase (eEF2K) expression, which activates PI3K signaling pathway ( 159 ). Also, oncosuppressor, miR-200b, activate target genes like SRY-box transcription factor 2 (SOX2), CD133, and zinc finger E-box binding homeobox 1 (ZEB1), aiding in migration and invasion and stemness ( 157 , 160 ).…”

Section: Non-coding Rna As Therapymentioning

confidence: 99%

Triple‑negative breast cancer: A run‑through of features, classification and current therapies (Review)

Manjunath

Choudhary

2021

Oncol Lett

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Section: Non-coding Rna As Therapymentioning

confidence: 99%

Triple‑negative breast cancer: A run‑through of features, classification and current therapies (Review)

Manjunath

Choudhary

2021

Oncol Lett

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“…In our study, silencing AC016405.3 significantly increased the expression of both miR‐576‐5p and miR‐22‐3p in MCF7 cells. Multiple studies demonstrated that miR‐22‐3p serves as an anti‐oncogenic gene in diverse cancers, 25 including BRCA 26,27 . Nakamura, Hayashi 28 found that the up‐regulation of miR‐22‐3p could increase radiosensitivity in cervical cancer.…”

Section: Discussionmentioning

confidence: 99%

AC016405.3 functions as an oncogenic long non‐coding RNA by regulating ERBB3 via sponging miR‐22‐3p in breast cancer

Wei

Wang

et al. 2021

Clinical Laboratory Analysis

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Background Increasing studies reported that long non‐coding RNAs are involved in regulating breast cancer (BRCA) progression. However, the specific roles and mechanisms of lncRNAs in BRCA remain largely unknown. Here, we sought to explore the functions and mechanisms of AC016405.3 in BRCA progression. Methods Bioinformatic analysis for AC016405.3, miR‐22‐3p, and ERBB3 were performed on starBase. The expressions of AC016405.3, miR‐22‐3p, and ERBB3 were examined by RT‐qPCR. The functions of AC016405.3 on the proliferation, migration, and invasion of cells were evaluated by conducting CCK‐8, colony formation, wound‐healing, and Transwell assays. The subcellular distribution of AC016405.3 in BRCA cells was identified by performing fluorescence in situ hybridization (FISH) and subcellular fractionation techniques. Dual‐luciferase assay was applied to validate the interactions of miR‐22‐3p with AC016405.3 or ERBB3. The interaction between ERBB3 and miR‐22‐3p was also tested by Anti‐Ago2 RNA immunoprecipitation (RIP) assay. Results The results showed that AC016405.3 is highly expressed in BRCA tissues as well as cells and positively correlated with poor prognosis in BRCA patients. Silencing AC016405.3 obviously repressed the malignant behaviors of BRCA cells. Mechanistically, AC016405.3 functioned as a competing endogenous RNA (ceRNA) for miR‐22‐3p in the cytoplasm and sponged miR‐22‐3p to release its suppression of ERBB3. Rescue experiments revealed that the suppression role induced by AC016405.3 depletion on malignant behaviors of BRCA cells could be obviously counter by inhibiting miR‐22‐3p or overexpressing ERBB3. Conclusion AC016405.3 promotes BRCA progression by the derepression of ERBB3 via sponging miR‐22‐3p, which may represent a potential target for BRCA treatment.

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“…The abnormal miRNA pro le of tumor cells accepted Everolimus treatment also supported corresponding targeted therapy strategies. And therapeutic intervention might be aimed at restoring normal miRNA levels 33 . Therefore, restoration of miR-7-5p could sensitize the effect of Everolimus.…”

Section: Discussionmentioning

confidence: 99%

Everolimus-Induced Loss of Exosomal miR-7-5p Activates MNK/eIF4E Axis in Non-Small Cell Lung Cancer

Liu

Wang

Ning

et al. 2021

Preprint

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Background: Everolimus is a kind of mTOR inhibitors. Activated mitogen-activated protein kinase interacting kinases/eukaryotic translation initiation factor 4E (MNK/eIF4E) axis plays a crucial role in resistance to Everolimus in non-small cell lung cancer cells (NSCLC). Typically, eIF4E phosphorylation increased by mTOR inhibitors was mainly mediated by MNKs. But the mechanisms are poorly understood. Recently, extensive reprogramming of miRNA profiles has also been found after long-term mTOR inhibitor exposing. Our previous studies have found that tumor suppressor miR-7-5p was loss in A549 cells after treatment of Everolimus. Exactly, MNK1 is the target of miR-7-5p. Here, we analyzed levels and functions of miR-7-5p in the usage of Everolimus in NSCLC.Methods: miR-7-5p level and expression of main markers of MNK/eIF4E axis was evaluated by qRT-PCR, in situ hybridization, and immunohistochemistry on human NPC samples, and by RT-PCR, western blot on NPC cell lines. Proliferation, migration and invasion of NPC cells in culture were assessed by Colony formation, CCK-8, Wound healing and Transwell assays. NPC cell tumorigenicity was assessed by xenotransplants in nude mice. Targeted binding of miR-7-5p to MNK1 was confirmed by the Dual-luciferase reporter assay. And the isolation and identification of exosomes were invested by Invitrogen™ Total Exosome RNA Isolation Kit, western blot, transmission electron microscopy and Zetasizer Nano ZS90 instrument.Results: Everolimus stimulatedtherelease of miR-7-5p loaded exosomes from NSCLC cellsinRab27A and Rab27B dependent manners, thereby reducing the intracellular tumor suppressor miR-7-5p to attenuate the inhibition of MNK1 and promote MNK-dependent eIF4E phosphorylation. Of note, both lower miR-7-5p and positive MNK1 could act as independent poor prognostic biomarkers for NSCLC. And delivery of miR-7-5p would inhibit the poor prognosis of it. Bothendogenous miR-7-5p-5p or exo-miR-7-5p collaborated with Everolimus, not only inhibited the proliferation, migration, and metastasisof NSCLC in vitro and in vivo, but also promoted the apoptosis of NSCLC viatargeting MNK/eIF4E axis.Conclusion: Everolimus-induced loss of exosomal miR-7-5p activates MNK/eIF4E axis to blunt effectiveness of itself in NSCLC. Therefore, delivery of miR-7-5p could act as a combined therapeutic strategy for mTOR-targeted cancer therapy and prognosis.

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ncRNA therapy with miRNA-22-3p suppresses the growth of triple-negative breast cancer

Cited by 36 publications

References 23 publications

Triple‑negative breast cancer: A run‑through of features, classification and current therapies (Review)

Triple‑negative breast cancer: A run‑through of features, classification and current therapies (Review)

AC016405.3 functions as an oncogenic long non‐coding RNA by regulating ERBB3 via sponging miR‐22‐3p in breast cancer

Everolimus-Induced Loss of Exosomal miR-7-5p Activates MNK/eIF4E Axis in Non-Small Cell Lung Cancer

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