MiR-92b-3p Inhibits Proliferation of HER2-Positive Breast Cancer Cell by Targeting circCDYL

Liang, Gehao; Ling, Yun; Lin, Qun; Shi, Yu; Luo, Qing; Cen, Yinghuan; Mehrpour, Maryam; Hamaï, Ahmed; Li, Jun; Gong, Chang

doi:10.3389/fcell.2021.707049

Cited by 12 publications

(11 citation statements)

References 30 publications

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“…HER2 is known to be involved in the proliferation, differentiation, invasion, and metastasis of cancer cells. − We assessed whether SignalTAC-mediated degradation could downregulate the downstream PI3K/AKT/mTOR signaling pathways and influence cell apoptosis and proliferation. We treated SKBR3 cells with SignalTACs (Ab1, Ab3, Ab4, or Ab6) or Tz under identical conditions and analyzed the levels of phosphorylated mTOR (p-mTOR), phosphorylated PI3K (p-PI3K) phosphorylated AKT (p-AKT), and phosphorylated HER2 (p-HER2).…”

Section: Resultsmentioning

confidence: 99%

Harnessing the Lysosomal Sorting Signals of the Cation-Independent Mannose-6-Phosphate Receptor for Targeted Degradation of Membrane Proteins

Tong

et al. 2023

J. Am. Chem. Soc.

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Membrane proteins are a crucial class of therapeutic targets that remain challenging to modulate using traditional occupancy-driven inhibition strategies or current proteolysis-targeting degradation approaches. Here, we report that the inherent endolysosomal sorting machinery can be harnessed for the targeted degradation of membrane proteins. A new degradation technique, termed signal-mediated lysosome-targeting chimeras (SignalTACs), was developed by genetically fusing the signaling motif from the cation-independent mannose-6-phosphate receptor (CI-M6PR) to a membrane protein binder. Antibody-based SignalTACs were constructed with the CI-M6PR signal peptides fused to the C-terminus of both heavy and light chains of IgG. We demonstrated the scope of this platform technology by degrading five pathogenesis-related membrane proteins, including HER2, EGFR, PD-L1, CD20, and CD71. Furthermore, two simplified constructs of SignalTACs, nanobody-based and peptide-based SignalTACs, were created and shown to promote the lysosomal degradation of target membrane proteins. Compared to the parent antibodies, SignalTACs exhibited significantly higher efficiency in inhibiting tumor cell growth both in vitro and in vivo. This work provides a simple, general, and robust strategy for degrading membrane proteins with molecular precision and may represent a powerful platform with broad research and therapeutic applications.

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Section: Resultsmentioning

confidence: 99%

Harnessing the Lysosomal Sorting Signals of the Cation-Independent Mannose-6-Phosphate Receptor for Targeted Degradation of Membrane Proteins

Tong

et al. 2023

J. Am. Chem. Soc.

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“…miRNAs are implicated in the regulation of various cellular activities during cancer progression, including proliferation and apoptosis 26,27 . Based on several previous studies, miR‐92b‐3p inhibits cell proliferation in HER2+ breast cancer, 28 and miR‐101‐5p acts as a tumor suppressor by inducing cell apoptosis in HER2+ breast cancer 29 . These studies suggested the important role of miRNAs in HER2+ breast cancer by affecting tumor cell proliferation and apoptosis.…”

Section: Discussionmentioning

confidence: 96%

“…miRNAs are implicated in the regulation of various cellular activities during cancer progression, including proliferation and apoptosis. 26,27 Based on several previous studies, miR-92b-3p inhibits cell proliferation in HER2+ breast cancer, 28 TFAP2C is a developmental regulatory gene that controls the early stage of ectodermal epidermal differentiation, and also exerts significant effects on mammary development and oncogenesis. 31,32 Studies have demonstrated that higher TFAP2C expression in breast cancer is associated with poor survival and potentially promoted tumor cell proliferation, suggesting that TFAP2C may be a potential drug target site.…”

Section: Discussionmentioning

confidence: 99%

KLF14/miR‐1283/TFAP2C axis inhibits HER2‐positive breast cancer progression via declining tumor cell proliferation

Chen

Luo

et al. 2023

Molecular Carcinogenesis

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MiR‐1283 has been identified as a tumor suppressor in some malignancies. Whereas, the role of miR‐1283 in HER2‐positive (HER2+) breast cancer, particularly its role in regulating cell proliferation, one of the most significant features of tumor progression, is unclear. The related microRNA screened by the breast cancer sample GSE131599 dataset were detected in HER2+ breast cancer tissues and cell lines. Then, the obtained miR‐1283 was overexpressed in SKBR3 and BT‐474 cells followed by relevant functional assays concerning cell proliferation and apoptosis. The xenograft mouse model was induced and the effect of miR‐1283 on tumor growth and cell proliferation was examined. The target of miR‐1283 and the transcription factor regulating miR‐1283 were predicted and identified. Finally, the influence of transcription factor KLF14 on cell proliferation and apoptosis was investigated. An integrated analysis confirmed that miR‐1283 expression was significantly decreased in HER2+ breast cancer tissues. Also, by q‐RT‐PCR detection, miR‐1283 expression was markedly reduced in HER2+ breast cancer tissues and cell lines. The miR‐1283 overexpression prevented the proliferation and enhanced apoptosis of HER2+ breast cancer cells, as well as inhibited tumor growth. Mechanistically, miR‐1283 inhibited TFAP2C expression by targeting the 3′‐untranslated regions of TFAP2C messenger RNA, and the KLF14 enhanced miR‐1283 level via binding to its promoter. The result subsequently confirmed the KLF14/miR‐1283 signaling suppressed cell proliferation in HER2+ breast cancer. Our results suggested that the KLF14/miR‐1283/TFAP2C axis inhibited HER2+ breast cancer progression, which might provide novel insight into mechanical exploration for this disease.

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“…Indeed, small RNA sequencing identified 88 upregulated miRNAs and 46 downregulated miRNAs in EVs from HPM culture compared to the DMEM culture. These 88 upregulated miRNAs included miRNAs that have been reported to suppress/inhibit tumor growth and metastasis such as miR-16-2-3p, miR-92b-3p, miR-197-3p, miR-204-5p, miR-320a, miR-411-5p, miR-424-5p, miR-708-5p, miR-718, miR-944, let-7a-5p, and let-7e-5p [52][53][54][55][56][57][58][59][60][61][62][63][64], suggesting that EVs from HPM culture may have superior anti-tumor effects. On the other hand, miRNAs known to protect articular cartilage and enhance cartilage regeneration such as miR-23a-3p, miR-26a-5p, miR-31-5p, miR-100-5p, and miR-140-3p are included in the 46 downregulated miRNAs [44,[65][66][67][68], suggesting that EVs from HPM culture may have less therapeutic effects in the treatment for osteoarthritis.…”

Section: Discussionmentioning

confidence: 99%

Culture Condition of Bone Marrow Stromal Cells Affects Quantity and Quality of the Extracellular Vesicles

Scheiber

Clark

Kaito

et al. 2022

IJMS

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Extracellular vesicles (EVs) released by bone marrow stromal cells (BMSCs) have been shown to act as a transporter of bioactive molecules such as RNAs and proteins in the therapeutic actions of BMSCs in various diseases. Although EV therapy holds great promise to be a safer cell-free therapy overcoming issues related to cell therapy, manufacturing processes that offer scalable and reproducible EV production have not been established. Robust and scalable BMSC manufacturing methods have been shown to enhance EV production; however, the effects on EV quality remain less studied. Here, using human BMSCs isolated from nine healthy donors, we examined the effects of high-performance culture media that can rapidly expand BMSCs on EV production and quality in comparison with the conventional culture medium. We found significantly increased EV production from BMSCs cultured in the high-performance media without altering their multipotency and immunophenotypes. RNA sequencing revealed that RNA contents in EVs from high-performance media were significantly reduced with altered profiles of microRNA enriched in those related to cellular growth and proliferation in the pathway analysis. Given that pre-clinical studies at the laboratory scale often use the conventional medium, these findings could account for the discrepancy in outcomes between pre-clinical and clinical studies. Therefore, this study highlights the importance of selecting proper culture conditions for scalable and reproducible EV manufacturing.

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MiR-92b-3p Inhibits Proliferation of HER2-Positive Breast Cancer Cell by Targeting circCDYL

Cited by 12 publications

References 30 publications

Harnessing the Lysosomal Sorting Signals of the Cation-Independent Mannose-6-Phosphate Receptor for Targeted Degradation of Membrane Proteins

Harnessing the Lysosomal Sorting Signals of the Cation-Independent Mannose-6-Phosphate Receptor for Targeted Degradation of Membrane Proteins

KLF14/miR‐1283/TFAP2C axis inhibits HER2‐positive breast cancer progression via declining tumor cell proliferation

Culture Condition of Bone Marrow Stromal Cells Affects Quantity and Quality of the Extracellular Vesicles

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