Targeted Inhibition of miR-221/222 Promotes Cell Sensitivity to Cisplatin in Triple-Negative Breast Cancer MDA-MB-231 Cells

Li, Shujun; Lu, Jianrong; Zhao, Qian; Li, Danni; Shen, Lei; Wang, Zhongrui; Liu, Junjun; Xie, Dacheng; Cho, William C.; Xu, Shaohua; Yu, Zuoren

doi:10.3389/fgene.2019.01278

Cited by 34 publications

(21 citation statements)

References 43 publications

(54 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…36 Additionally, miR-222 has been reported to promote the resistance of the breast cancer cell line MDA-MB-231 to carboplatin. 38 Although there is apparently no report on the effect of miR-222 on resistance to etoposide, a study did show that miR-222 advanced the resistance of SGC7901 cells to radiotherapy in gastric cancer epithelial cells by targeting PTEN, 39 and the PTEN/phosphatidylinositol 3-kinase Comparisons among multiple groups were conducted by ANOVA with Tukey's post hoc test. Statistical analysis in relation to time-based measurements within each group was conducted using repeated-measures ANOVA followed by a Bonferroni's post hoc test.…”

Section: Discussionmentioning

confidence: 99%

“… 36 Additionally, miR-222 has been reported to promote the resistance of the breast cancer cell line MDA-MB-231 to carboplatin. 38 Although there is apparently no report on the effect of miR-222 on resistance to etoposide, a study did show that miR-222 advanced the resistance of SGC7901 cells to radiotherapy in gastric cancer epithelial cells by targeting PTEN, 39 and the PTEN/phosphatidylinositol 3-kinase signaling pathway plays an important role in etoposide resistance. 40 We are convinced that a high level of miR-222 will still result in drug resistance with regard to the combination of three drugs used for RB treatment, but it is resistant to different drugs through different signaling pathways.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

microRNA-222-Mediated VHL Downregulation Facilitates Retinoblastoma Chemoresistance by Increasing HIF1α Expression

Zhao

Sun

2020

Invest. Ophthalmol. Vis. Sci.

View full text Add to dashboard Cite

PURPOSE. Retinoblastoma (RB) is the most common primary intraocular tumor in children. Chemoresistance is the major obstacle for treatment of these tumors. This study aims to determine whether or not downregulating microRNA-222 (miR-222) could serve as a potential therapeutic target for preventing chemoresistance in RB treatment. METHODS. Differentially expressed miR-222 in RB samples and its downstream target genes were predicted using bioinformatics methods. The expression of miR-222 was altered by mimic or inhibitor to examine its role in RB cell in response to the chemotherapeutic agent vincristine (VCR). Further bioinformatic analysis predicted involvement of the stability of hypoxia-inducible factor 1α (HIF1α) protein in regulation of the von Hippel-Lindau (VHL) tumor suppressor, followed by characterization of the effect of VHL on the ubiquitin-proteasome degradation of HIF1α. Next, VHL or HIF1α was overexpressed to determine their effects on RB cell activities after VCR treatment. In vivo assays were performed on nude mice to further verify the in vitro results. RESULTS. miR-222 is highly expressed in RB tissues and cells and was found to facilitate resistance of RB cells to VCR. Of note, miR-222 specifically bound to and negatively regulated VHL. VHL could inhibit the stability of HIF1α and promote the degradation of ubiquitin-proteasome, thus reducing HIF1α expression to attenuate VCR resistance in RB cells. Moreover, inhibition of miR-222 in combination with VCR suppressed tumor formation in nude mice. CONCLUSIONS. miR-222 promotes the expression of HIF1α by targeting VHL, thus accelerating the resistance of RB cells to the chemotherapeutic agent VCR.

show abstract

Section: Discussionmentioning

confidence: 99%

“… 36 Additionally, miR-222 has been reported to promote the resistance of the breast cancer cell line MDA-MB-231 to carboplatin. 38 Although there is apparently no report on the effect of miR-222 on resistance to etoposide, a study did show that miR-222 advanced the resistance of SGC7901 cells to radiotherapy in gastric cancer epithelial cells by targeting PTEN, 39 and the PTEN/phosphatidylinositol 3-kinase signaling pathway plays an important role in etoposide resistance. 40 We are convinced that a high level of miR-222 will still result in drug resistance with regard to the combination of three drugs used for RB treatment, but it is resistant to different drugs through different signaling pathways.…”

Section: Discussionmentioning

confidence: 99%

microRNA-222-Mediated VHL Downregulation Facilitates Retinoblastoma Chemoresistance by Increasing HIF1α Expression

Zhao

Sun

2020

Invest. Ophthalmol. Vis. Sci.

View full text Add to dashboard Cite

show abstract

“…In the current study, we are the first to demonstrate that Reck gene, a direct target of miR-221/222, is an important mediator for the miR-221/222-induced CSC properties, and verify the involvement of Reck gene in the epigenetic regulation of CSCs. Our previous work has demonstrated the oncogenic function of miR-221/222 in regulating the cellular migration, invasion, CSCs and drug-resistance in triple negative breast cancer (Li et al, 2014(Li et al, , 2020. However, the regulatory function and mechanism of miR-221/222 in lung CSCs remain unclear.…”

Section: Discussionmentioning

confidence: 99%

Reck-Notch1 Signaling Mediates miR-221/222 Regulation of Lung Cancer Stem Cells in NSCLC

Guo

Wang²,

Wang³

et al. 2021

Front. Cell Dev. Biol.

Self Cite

View full text Add to dashboard Cite

Cancer stem cells (CSCs) contribute to the cancer initiation, metastasis and drug resistance in non-small cell lung cancer (NSCLC). Herein, we identified a miR-221/222 cluster as a novel regulator of CSCs in NSCLC. Targeted overexpression or knockdown of miR-221/222 in NSCLC cells revealed the essential roles of miR-221/222 in regulation of lung cancer cell proliferation, mammosphere formation, subpopulation of CD133+ CSCs and the expression of stemness genes including OCT4, NANOG and h-TERT. The in vivo animal study showed that overexpression of miR-221/222 significantly enhanced the capacity of lung cancer cells to develop tumor and grow faster, indicating the importance of miR-221/222 in tumorigenesis and tumor growth. Mechanistically, Reck was found to be a key direct target gene of miR-221/222 in NSCLC. Overexpression of miR-221/222 significantly suppressed Reck expression, activated Notch1 signaling and increased the level of NICD. As an activated form of Notch1, NICD leads to enhanced stemness in NSCLC cells. In addition, knockdown of Reck by siRNA not only mimicked miR-221/222 effects, but also demonstrated involvement of Reck in the miR-221/222-induced activation of Notch1 signaling, verifying the essential roles of the miR-221/222-Reck-Notch1 axis in regulating stemness of NSCLC cells. These findings uncover a novel mechanism by which lung CSCs are significantly manipulated by miR-221/222, and provide a potential therapeutic target for the treatment of NSCLC.

show abstract

“…For instance, p53 is a apoptosis-related factor that can function as an upstream mediator of PTEN in cancer therapy [ 210 ]. The combination of anti-miRNA-222/221 with cisplatin induces p53 expression to stimulate PTEN, resulting in increased efficacy in the eradication of triple-negative breast cancer cells [ 211 ].…”

Section: Microrna and Pten Relationshipmentioning

confidence: 99%

Small in Size, but Large in Action: microRNAs as Potential Modulators of PTEN in Breast and Lung Cancers

et al. 2021

View full text Add to dashboard Cite

MicroRNAs (miRNAs) are well-known regulators of biological mechanisms with a small size of 19–24 nucleotides and a single-stranded structure. miRNA dysregulation occurs in cancer progression. miRNAs can function as tumor-suppressing or tumor-promoting factors in cancer via regulating molecular pathways. Breast and lung cancers are two malignant thoracic tumors in which the abnormal expression of miRNAs plays a significant role in their development. Phosphatase and tensin homolog (PTEN) is a tumor-suppressor factor that is capable of suppressing the growth, viability, and metastasis of cancer cells via downregulating phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling. PTEN downregulation occurs in lung and breast cancers to promote PI3K/Akt expression, leading to uncontrolled proliferation, metastasis, and their resistance to chemotherapy and radiotherapy. miRNAs as upstream mediators of PTEN can dually induce/inhibit PTEN signaling in affecting the malignant behavior of lung and breast cancer cells. Furthermore, long non-coding RNAs and circular RNAs can regulate the miRNA/PTEN axis in lung and breast cancer cells. It seems that anti-tumor compounds such as baicalein, propofol, and curcumin can induce PTEN upregulation by affecting miRNAs in suppressing breast and lung cancer progression. These topics are discussed in the current review with a focus on molecular pathways.

show abstract

Targeted Inhibition of miR-221/222 Promotes Cell Sensitivity to Cisplatin in Triple-Negative Breast Cancer MDA-MB-231 Cells

Cited by 34 publications

References 43 publications

microRNA-222-Mediated VHL Downregulation Facilitates Retinoblastoma Chemoresistance by Increasing HIF1α Expression

microRNA-222-Mediated VHL Downregulation Facilitates Retinoblastoma Chemoresistance by Increasing HIF1α Expression

Reck-Notch1 Signaling Mediates miR-221/222 Regulation of Lung Cancer Stem Cells in NSCLC

Small in Size, but Large in Action: microRNAs as Potential Modulators of PTEN in Breast and Lung Cancers

Contact Info

Product

Resources

About