MicroRNA signatures in chemotherapy resistant esophageal cancer cell lines

Hummel, Richard; Sie, Corina; Watson, David I.; Wang, Tingting; Ansar, Alfiya; Michael, Michael; Hoek, Mark Van der; Haier, Joerg; Hussey, Damian J.

doi:10.3748/wjg.v20.i40.14904

Cited by 69 publications

(71 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although LY6K is not known as a transcriptional factor, transcription of miR-192-5p might be indirectly promoted by ectopic expression of LY6K. Recently, miR-192-5p was also identified as a potential target for esophageal cancer cells in a study profiling the development of chemotherapy resistance [26]. We observed that miR-192-5p was related to tamoxifen resistance through cell viability and apoptosis in breast cancer cells (Figure 6).…”

Section: Discussionmentioning

confidence: 79%

miRNAs involved in LY6K and estrogen receptor α contribute to tamoxifen-susceptibility in breast cancer

et al. 2016

View full text Add to dashboard Cite

Estrogen receptor-alpha (ERα) is a clinically important therapeutic target for breast cancer. However, tumors that lose ERα are less responsive to anti-estrogens such as tamoxifen. MicroRNAs (miRNAs) are small RNAs that regulate expression of their target gene and dysregulations of miRNA has been identified in many diseases including human cancer. However, only a few miRNAs associated with tamoxifen resistance has been reported. In this study, we found that lymphocyte antigen 6 complex (LY6K), which is a member of the Ly-6/μPAR superfamily and related to breast cancer progression and metastasis, is inversely correlated with ERα expression. We, for the first time, found miRNAs involved in the regulatory molecular mechanism between ERα and LY6K and related to tamoxifen susceptibility in breast cancer. miR-192-5p, induced by LY6K, downregulates ERα directly and induced tamoxifen resistance in ERα-positive breast cancer cells. In addition, re-expression of ERα in ERα-negative breast cancer cells increased miR-500a-3p expression and directly inhibits LY6K expression. Ectopic expression of miR-500a-3p sensitized ERα-negative cells to tamoxifen by increasing apoptosis. Finally, we observed an inverse correlation between LY6K and ERα in primary breast cancer samples. We found that patients with recurrence showed high expression of miR-192-5p after tamoxifen treatments. In addition, expression of miR-500a-3p was significantly correlated to survival outcome. As miRNAs involved in the regulatory mechanism between LY6K and ERα can affect tamoxifen resistance, downregulating miR-192-5p or re-expressing miR-500a-3p could be a potential therapeutic approach for treating tamoxifen resistant patients.

show abstract

Section: Discussionmentioning

confidence: 79%

miRNAs involved in LY6K and estrogen receptor α contribute to tamoxifen-susceptibility in breast cancer

et al. 2016

View full text Add to dashboard Cite

show abstract

“…In cisplatin resistant ESCC cells, miR-130a-3p was increased, and in 5-FU (5-fluorouracil) resistant esophageal cancer cells, miR-378a-3p, miR-192-5p, miR-210-3p, miR-194-5p, miR-17-3p, miR-935, miR-125a-5p, miR-1226-3p, miR-99b-5p, and miR-18a-3p were significantly down-regulated, while miR-222-3p, miR193b-3p, miR-31-5p, miR-27b-3p, and miR-550a-3p were increased. The results from this extensive study clearly demonstrate that esophageal cancer cells have distinct miRNA expression profiles that differentially affect response to individual chemotherapeutic agents [29]. We found that miR193a-5p down-regulation was significantly associated with poor prognosis in ESCC patients (Figure 4).…”

Section: Discussionmentioning

confidence: 67%

MiR-193a-5p/ERBB2 act as concurrent chemoradiation therapy response indicator of esophageal squamous cell carcinoma

et al. 2016

View full text Add to dashboard Cite

Concurrent chemoradiation therapy (CCRT) is the predominant treatment in esophageal cancer, however resistance to therapy and tumor recurrence are exceedingly common. Elevated ERBB2/Her2 may be at least partially responsible for both the high rates of recurrence and resistance to CCRT. This receptor tyrosine kinase is upregulated in 10–20% of esophageal squamous cell carcinoma (ESCC) tissues, and amplification of ERBB2 has been correlated with poor prognosis in esophageal cancer. Tissues from 131 ESCC patients, along with cell and animal models of the disease were used to probe the underlying mechanisms by which ERBB2 upregulation occurs and causes negative outcomes in ESCC. We found that overexpression of ERBB2 inhibited radiosensitivity in vitro. Furthermore, miR-193a-5p reduced ERBB2 expression by directly targeting the 3′UTR. Increased miR-193a-5p enhanced radiosensitivity and inhibited tumorigenesis in vitro and in vivo. Additionally, low miR-193a-5p expression correlated with poor prognosis in ESCC patients, and ESCC patients with good CCRT response exhibited higher miR-193a-5p expression. Our data suggest that patients with high miR-193a-5p will likely benefit from CCRT treatment alone, however a combination of CCRT with Herceptin may be beneficial for patients with low miR-193a-5p expression.

show abstract

“…However, Dinicola et al (41) reported that the final concentration of 5-FU could refer to the clinical plasma concentration of 2.0 µg/ml. The other commonly used method is the pulse treatment method, which was described by Hummel et al (30) with a relatively low-dose of 5-FU (0.65 µg/ml). The resistant cells selected by the intermittent incremental method were more resistant than the cells selected by the pulse method (42).…”

Section: Discussionmentioning

confidence: 99%

“…As for ESCC 5-FU-resistant cells, TE-5 (8), TE-11 (27), KYSE410 (28) and KYSE150 (29) have been reported, and their drug resistance mechanisms have also been studied. Compared with tumor parental cells, 5-FU-resistant ESCC cells were found to exhibit upregulation of DPD (8) and PI3K/AKT (29), specific miRNA signatures (30), and the activation of Id1-E2F1-IGF2/ TS (28). To overcome resistance to 5-FU, researchers have demonstrated that photodynamic therapy (PDT) could induce potent cytotoxicity in 5-FU-resistant ESCC cells (TE-5R and TE-11R) independent of their differentiation grade or 5-FU resistance (27).…”

Section: Introductionmentioning

confidence: 99%

A novel 5-fluorouracil-resistant human esophageal squamous cell carcinoma cell line Eca-109/5-FU with significant drug resistance-related characteristics

Zhang

Shi

et al. 2017

Oncology Reports

View full text Add to dashboard Cite

5-Fluorouracil (5-FU) is used for the clinical treatment of esophageal squamous cell carcinomas (ESCCs), yet it also induces chemoresistant cancer cells during treatment, which leads to the failure of the therapy. To further explore the resistance mechanism of 5-FU in ESCC, we established the 5-FU-resistant ESCC cell line Eca-109/5-FU, which was prepared by the stepwise exposure to increasing 5-FU concentrations. MTT assay and nude mouse xenograft models were used to test the drug resistance and proliferation of Eca-109 and Eca-109/5-FU cells in vitro and in vivo. Apoptosis and cell cycle distribution were determined using flow cytometry. Drug resistance-related proteins were detected by western blotting. Metabolomic profiles were obtained from nuclear magnetic resonance (NMR) tests. In regards to Eca-109/5-FU, the decreased susceptibility to 5-FU was determined in vitro and in vivo with slower rate of proliferation. Drug resistance-related proteins (multidrug resistance-associated protein 1 and ATP-binding cassette superfamily G member 2), epithelial-to-mesenchymal transition (EMT)-related proteins (E-cadherin and vimentin) and cancer stem cell-related proteins (prominin-1 and hyaluronate receptor) exhibited significant differences between the two cell lines. The 5-FU-resistant cell line Eca-109/5-FU achieved the ability to tolerate 5-FU, which may depend on significant drug resistance-related characteristics, such as EMT and cancer stem cell-like properties. The metabolism of Eca-109/5-FU was altered, and more than 15 metabolites was found to contribute to the difference in the metabolite profile, such as lactate, glutamate, taurine, glutamine, proline, aspartate, methanol, cystine, glycine and uracil. Our results identified that the resistant cell line Eca-109/5-FU showed quite different characteristics compared with the parental Eca-109 cells. The Eca-109/5-FU cell line provides an experimental model for further steps to select chemotherapeutic sensitizers.

show abstract

MicroRNA signatures in chemotherapy resistant esophageal cancer cell lines

Abstract: The current study supports the hypothesis that microRNA expression has an impact on chemotherapy resistance in esophageal cancer.

Cited by 69 publications

References 28 publications

miRNAs involved in LY6K and estrogen receptor α contribute to tamoxifen-susceptibility in breast cancer

miRNAs involved in LY6K and estrogen receptor α contribute to tamoxifen-susceptibility in breast cancer

MiR-193a-5p/ERBB2 act as concurrent chemoradiation therapy response indicator of esophageal squamous cell carcinoma

A novel 5-fluorouracil-resistant human esophageal squamous cell carcinoma cell line Eca-109/5-FU with significant drug resistance-related characteristics

Contact Info

Product

Resources

About