Nkx-2.5 Regulates MDR1 Expression via Its Upstream Promoter in Breast Cancer Cells

Lim, Jung-Suk; Jung, Gyu Yeon; Park, Seung-Yoon

doi:10.3346/jkms.2019.34.e100

Cited by 6 publications

(5 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…There have also been prior reports linking SNHG7 to chemoresistance, as in the study conducted by Chen et al ( 37 ) who observed the overexpression of this lncRNA in 26 DDP-resistant NSCLC tumors, with loss- and gain-of-function analyses confirming that higher SNHG7 expression levels promote DDP-resistance in these cancer cells. Mechanistically, SNHG7 silencing suppresses p-glycoprotein (MDR1) expression ( 38 ), ATP binding cassette subfamily G member 2 (BCRP) expression ( 39 ), and PI3K/AKT/mTOR pathway activation ( 40 ), all of which are related to chemoresistance. In this report, DDP-resistant NSCLC patient tumor tissues and cell lines exhibited marked SNHG7 upregulation, and the knockdown of this lncRNA confirmed its role as a promoter of NSCLC cell motility, proliferation, and resistance to DDP treatment.…”

Section: Discussionmentioning

confidence: 99%

LncRNA SNHG7 promotes non-small cell lung cancer progression and cisplatin resistance by inducing autophagic activity

She¹,

He²,

Xiao³

et al. 2023

J Thorac Dis

View full text Add to dashboard Cite

Background Cisplatin (DDP) is among the most widely used chemotherapeutic drugs for non-small cell lung cancer (NSCLC), yet the frequent emergence of chemoresistance serves as a major barrier to the treatment of this tumor type. Long non-coding RNAs (lncRNAs) have recently been shown to influence the ability of cells to resist particular chemotherapy drugs. The present study was developed to explore the role of the lncRNA SNHG7 as a regulator of NSCLC cell chemosensitivity. Methods Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to measure SNHG7 expression in NSCLC tissues from patients that were sensitive/resistant to DDP, correlations between SNHG7 expression levels and the patients’ clinicopathological characteristics were assessed, and the prognostic relevance of SNHG7 expression was examined via the Kaplan-Meier approach. In addition, SNHG7 expression was assessed in NSCLC cell lines that were DDP-sensitive or -resistant, while western blotting and immunofluorescence staining were employed to detect autophagy-associated protein expression in A549, A549/DDP, HCC827, and HCC827/DDP cells. NSCLC cell chemoresistance was quantified via the Cell Counting Kit-8 (CCK-8) assay approach, and flow cytometry was used to detect the apoptotic death of these tumor cells. The chemosensitivity of xenograft tumors in vivo was further assessed to validate the functional importance of SNHG7 as a regulator of NSCLC DDP resistance. Results Relative to paracancerous tissues, NSCLC tumors exhibited SNHG7 upregulation, and this lncRNA was further upregulated in DDP-resistant patients compared to chemosensitive patients. Consistently, higher SNHG7 expression levels were correlated with worse patient survival outcomes. DDP-resistant NSCLC cells were also found to exhibit higher levels of SNHG7 expression than chemosensitive cells, and knocking down this lncRNA enhanced the sensitivity of these cells to DDP treatment, resulting in impaired proliferation and higher rates of apoptotic death. Knocking down SNHG7 was also sufficient to suppress microtubule associated protein 1 light chain 3 beta (LC3B) and Beclin1 protein levels and promote p62 upregulation in vitro . The silencing of this lncRNA additionally inhibited the resistance of NSCLC xenograft tumors to DDP treatment in vivo. Conclusions SNHG7 can promote malignant behaviors and DDP resistance in NSCLC cells at least partly via the induction of autophagic activity.

show abstract

Section: Discussionmentioning

confidence: 99%

LncRNA SNHG7 promotes non-small cell lung cancer progression and cisplatin resistance by inducing autophagic activity

She¹,

He²,

Xiao³

et al. 2023

J Thorac Dis

View full text Add to dashboard Cite

show abstract

“…Cole et al в 1992 году открыли белок множественной лекарственной устойчивости (MDR1 или Pgp), который функционирует как аденозин-5-фосфатаза ATP-зависимая помпа для цитотоксических препаратов [18,19]. Он транспортирует отрицательно заряженные ионы, конъюгированные с молекулой глутатиона, обеспечивая резистентность к препаратам платины [20]. При отсутствии экспрессии в 100% случаев ответ на химиотерапию наблюдался в 96% случаев.…”

Section: Discussionunclassified

ABC transporters in the development of platinum drug resistance in serous ovarian carcinoma

Ulyanova¹,

Nepomnyashchaya²,

Zhukova³

et al. 2022

Clin. Exp.Morphology

View full text Add to dashboard Cite

Introduction. Serous ovarian carcinoma is a group of extremely aggressive malignant tumors with high mortality rates; today, it remains the most prognostically unfavorable gynecologic cancer in the world. One of the causes is the development of multidrug resistance after administration of various chemotherapy regimens. Therefore, the search for effective markers of resistance to chemotherapy in this disease is promising. The purpose of this study was to analyze expressions of ABC transporters Pgp (ABCB1) and BCRP (ABCG2) in cells of high-grade serous ovarian carcinomas in patients with varying sensitivity to platinum-based polychemotherapy. Materials and methods. Tumor tissues of 100 patients aged 29–79 years with high-grade serous ovarian carcinomas and stages IIIC–IV were studied with immunohistochemical method with rabbit P-glycoprotein 1 (Pgp or MDR1) polyclonal antibodies and by the Reveal Polyvalent HRP-DAB Detection System with mouse monoclonal BCRP antibodies (JF0994 clone). We used the Statistica 13.0 program (StatSoftInc., USA) to analyze the results. We determined the Mann–Whitney U and Pearson’s χ² values, as well as odds ratios with CI. Results. In groups with platinum resistance and platinum sensitivity, there prevailed patients with Pgp+ (98% and 68%) and BCRP+ (90% and 81.4%). Mann–Whitney U-test showed that in cancer cells in platinum-resistant patients, the expression of Pgp and BCRP (70;40–100 and 65;45–90) was 1.8 (p=0.003) and 1.9 times (p=0.013) higher, respectively, than in platinum-sensitive patients (40;4–65 and 35;10–60). Conclusion. The results on the Pgp marker show that it can be used as a predictive factor in high-grade serous ovarian carcinomas. Keywords: serous ovarian carcinoma, multidrug resistance, ABC transporters, Pgp, BCRP

show abstract

“…Among the subset of C2 pathways related to cancer, enriched pathways pointed to association of high BORG expression levels with high grade cancer phenotypes (Figure 4B,C). We showed that targets of a number of key carcinogenic transcription factors were enriched amongst genes upregulated in high BORG-expressing cells (Figure 4D), including those associated with metastasis and invasive phenotype (FOXD1, EVI1/MECOM, MEF2C), EMT (EVI1/MECOM, OCT1/POU2F1, MEF2A), brain metastasis (MEF2C), poor prognosis (FOXD1), and multi-drug resistance (NKX-2.5) [46][47][48][49][50][51][52][53] (Figure 4D,E,F). Interestingly, our previous work in murine models of breast cancer development and metastatic progression demonstrated robust acquisition of pro-metastatic and drug-resistance phenotypes following BORG overexpression 38,40,42 .…”

Section: Induction Of Invasive Signatures In High Borg-expressing Tnb...mentioning

confidence: 99%

Induction of Invasive Basal Phenotype in Triple-Negative Breast Cancers by Long Noncoding RNA BORG

Niazi,

Parker,

Mason

et al. 2024

Preprint

View full text Add to dashboard Cite

Long noncoding RNAs (lncRNAs) are known to play key roles in breast cancers; however, detailed mechanistic studies of lncRNA function have not been conducted in large cohorts of breast cancer tumors, nor have inter-donor and inter-subtype variabilities been taken into consideration. Here we provide the first identification and annotation of the human BORG lncRNA gene. Using multiple tumor cohorts of human breast cancers, we show that while BORG expression is strongly induced in breast tumors as compared to normal breast tissues, the extent of BORG induction varies widely between breast cancer subtypes and even between different tumors within the same subtype. Elevated levels of BORG in breast tumors are associated with the acquisition of core cancer aggression pathways, including those associated with basal tumor and pluripotency phenotypes, and with epithelial-mesenchymal transition (EMT) programs. While a subset of BORG-associated pathways was present in high BORG-expressing tumors across all breast cancer subtypes, many were specific to triple-negative breast cancer tumors. Finally, we show that genes induced by heterologous expression of BORG in murine models of TNBC both in vitro and in vivo strongly overlap with those associated with high BORG levels in human TNBC tumors, indicating that human BORG is a novel driver of the highly aggressive basal TNBC tumor phenotype.

show abstract

Nkx-2.5 Regulates MDR1 Expression via Its Upstream Promoter in Breast Cancer Cells

Cited by 6 publications

References 29 publications

LncRNA SNHG7 promotes non-small cell lung cancer progression and cisplatin resistance by inducing autophagic activity

LncRNA SNHG7 promotes non-small cell lung cancer progression and cisplatin resistance by inducing autophagic activity

ABC transporters in the development of platinum drug resistance in serous ovarian carcinoma

Induction of Invasive Basal Phenotype in Triple-Negative Breast Cancers by Long Noncoding RNA BORG

Contact Info

Product

Resources

About