Publications by authors named "Qianni Jin"

7 Publications

  • Page 1 of 1

The miR-186-3p/EREG axis orchestrates tamoxifen resistance and aerobic glycolysis in breast cancer cells.

Oncogene 2019 07 9;38(28):5551-5565. Epub 2019 Apr 9.

Key Laboratory of Diagnostic Medicine Designated by the Ministry of Education, Chongqing Medical University, 400016, Chongqing, China.

Tamoxifen resistance is one of the major challenges for its medical uses in estrogen receptor (ER)-positive breast cancer. Aerobic glycolysis, an anomalous characteristic of glucose metabolism in cancer cells, has been shown to associate with the resistance to chemotherapeutic agents. It remains, however, largely unclear whether and how tamoxifen resistance contributes to aerobic glycolysis in breast cancer. Here, we report that tamoxifen resistance is associated with enhanced glycolysis in ER-positive breast cancer cells. We demonstrate that EREG, an agonist of EGFR, has an important role in enhancing glycolysis via activating EGFR signaling and its downstream glycolytic genes in tamoxifen-resistant breast cancer cells. We further show that EREG is a direct target of miR-186-3p and that downregulation of miR-186-3p by tamoxifen results in EREG upregulation in tamoxifen-resistant breast cancer cells. Importantly, systemic delivery of cholesterol-modified agomiR-186-3p to mice bearing tamoxifen-resistant breast tumors effectively attenuates both tumor growth and [F]-fluoro-deoxyglucose ([F]-FDG) uptake. Together, our results reveal a novel molecular mechanism of resistance to hormone therapies in which the miR-186-3p/EREG axis orchestrates tamoxifen resistance and aerobic glycolysis in ER-positive breast cancer, suggesting targeting miR-186-3p as a promising strategy for therapeutic intervention in endocrine-resistant breast tumors.
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http://dx.doi.org/10.1038/s41388-019-0817-3DOI Listing
July 2019

[Verteporfin inhibits proliferation, invasion and migration of MDA-MB-231 human breast cancer cells by down-regulating the expression of Yes-associated protein].

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 2017 Sep;33(9):1223-1227

Ministry of Education Key Laboratory of Laboratory Medical Diagnostics, Chongqing Medical University, Chongqing 400016, China. *Corresponding author, E-mail:

Objective To investigate the effects of verteporfin on the proliferation, invasion and migration of human breast cancer MDA-MB-231 cells and the underlying mechanism. Methods MDA-MB-231 cells in the logarithmic growth phase were randomly divided into control group and verteporfin treatment group. After MDA-MB-231 cells were treated with (0, 4, 8, 12, 16) μmol/mL verteporfin, the minimal inhibitory concentration was determined by CCK-8 assay. After treatment with 4 μmol/mL verteporfin, the invasion and migration abilities of MDA-MB-231 cells were detected by Transwell invasion assay and scratch wound healing assay, respectively. The expression levels of proliferation-associated proteins c-MYC, cyclin D1, Yes-associated protein (YAP), cysteine-rich protein 61 (CYR61) and connective tissue growth factor (CTGF) in MDA-MB-231 cells treated by (0, 4, 8, 12, 16) μmol/mL verteporfin were determined by Western blotting. Results Verteporfin markedly inhibited the proliferation of MDA-MB-231 cells in a dose-dependent manner, and the minimal inhibitory concentration was 4 μmol/mL. The 4 μmol/mL verteporfin significantly inhibited the invasion and migration abilities of MDA-MB-231 cells. Verteporfin inhibited significantly the expressions of c-MYC, cyclin D1, YAP, CYR61 and CTGF. Conclusion Verteporfin significantly inhibits the proliferation, invasion and migration of MDA-MB-231 cells by down-regulating the expressions of YAP and its target genes CYR61 and CTGF.
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September 2017

Cisplatin-induced autophagy protects breast cancer cells from apoptosis by regulating yes-associated protein.

Oncol Rep 2017 Dec 16;38(6):3668-3676. Epub 2017 Oct 16.

Key Laboratory of Diagnostic Medicine Designated by the Ministry of Education, Chongqing Medical University, Yuzhong, Chongqing 400016, P.R. China.

Breast cancer is a common cause of cancer‑related deaths in women. Treatment with cisplatin exhibits some therapeutic efficacy. However, treatment optimization is required, and the mechanisms underlying the cisplatin's proapoptotic effects remain unclear. In the present study, we demonstrated that cisplatin induced apoptosis and autophagy in breast cancer cells. Autophagy induced by cisplatin played a protective role in breast cancer cells, which impaired its proapoptotic effect. Mechanistically, for the first time, we found that cisplatin treatment activated the MAPK signaling pathway and promoted autophagy via the ERK signaling pathway. Notably, we found that nuclear translocation of yes-associated protein (YAP) was regulated by cisplatin-induced autophagy, and we identified YAP as a survival input that promoted survival in cisplatin-treated breast cancer cells. These findings revealed that administration of cisplatin along with an autophagy inhibitor is a promising therapeutic strategy for treating breast cancer.
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http://dx.doi.org/10.3892/or.2017.6035DOI Listing
December 2017

Leptin promotes the migration and invasion of breast cancer cells by upregulating ACAT2.

Cell Oncol (Dordr) 2017 Dec 2;40(6):537-547. Epub 2017 Aug 2.

Department of Otolarynology, Chongqing Medical University, Chongqing, 400016, China.

Background: Previously, it has been shown that obesity may be considered as a risk factor for breast cancer in postmenopausal women. Leptin, a hormone whose level is elevated in obesity, has been suggested to be involved in the development of breast cancer, and univariate survival analyses have shown that over-expression of ACAT2, an enzyme that is involved in the production of cholesteryl esters, may be associated with a poor prognosis. Here, we aimed to investigate the effect of leptin on the proliferation, migration and invasion of breast cancer cells, as well as to elucidate its underlying mode of action.

Methods: Gene expression changes in leptin treated breast cancer-derived MCF-7, T47D and BT474 cells were assessed using PCR array, qRT-PCR and Western blot analyses. The expression patterns of Ob-R (leptin receptor) and ACAT2 in breast cancer cells and primary breast cancer tissue samples were analyzed using immunofluorescence and immunohistochemistry, respectively. Leptin-induced proliferation of breast cancer cells was assessed using a CCK8 assay, and scratch wound and Transwell assays were used to assess breast cancer cell invasion and migration.

Results: We found that, among the genes tested, ACAT2 expression exhibited the most significant changes in the leptin treated cells. In addition, we found that inhibition of ACAT2 expression using pyripyropene A (PPPA) or siRNA-mediated gene silencing significantly decreased leptin-induced proliferation, migration and invasion of MCF-7 and T47D cells. Subsequent Western blot analyses strongly indicated that the PI3K/AKT/SREBP2 signaling pathway was involved in leptin-induced ACAT2 upregulation in both MCF-7 and T47D cells. Finally, through the analysis of primary breast cancer tissue samples we found that ACAT2 may affect cancer progression through activation of the Ob-R.

Conclusions: Our data indicate that leptin may enhance the proliferation, migration and invasion of breast cancer cells via ACAT2 up-regulation through the PI3K/AKT/SREBP2 signaling pathway. Therefore, the leptin/ACAT2 axis may represent an attractive therapeutic target for breast cancer, particularly in postmenopausal and/or obese women.
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http://dx.doi.org/10.1007/s13402-017-0342-8DOI Listing
December 2017

Pyruvate kinase M2 interacts with mammalian sterile 20-like kinase 1 and inhibits tamoxifen-induced apoptosis in human breast cancer cells.

Tumour Biol 2017 Apr;39(4):1010428317692251

1 Key Laboratory of Diagnostic Medicine Designated by the Ministry of Education, Chongqing Medical University, Chongqing, China.

Tamoxifen has been reported to be associated with antagonism of estrogen-mediated cell growth signaling and activation of estrogen receptor-independent apoptosis events. It has been demonstrated that mammalian sterile 20-like kinase 1 is a direct target of Caspases to amplify the apoptotic signaling pathway. Here, we presented that breast cancer MCF-7 and SKBR3 cells under treatment with 4-hydroxytamoxifen displayed decreased level of pyruvate kinase M2. Western blot results also showed that 4-hydroxytamoxifen induced the activity of pro-apoptotic protein Caspase-3 in MCF-7 and SKBR3 cells, as evidenced by the cleavage of mammalian sterile 20-like kinase 1 substrate in a dose-dependent manner. Co-immunoprecipitation and immunofluorescence experiments were performed to clarify the relationship between pyruvate kinase M2 and mammalian sterile 20-like kinase 1. The results indicated that mammalian sterile 20-like kinase 1 was associated with pyruvate kinase M2 in cultured mammalian cells, and the interaction between mammalian sterile 20-like kinase 1 and pyruvate kinase M2 was decreased in response to 4-hydroxytamoxifen treatment. In addition, knockdown of pyruvate kinase M2 upregulated the level of cleaved Caspase-3 and subsequently facilitated the nuclear translocation of mammalian sterile 20-like kinase 1. Our data further supplemented the extensive functions of pyruvate kinase M2 in mediating breast cancer cell viability by substantially abating the mammalian sterile 20-like kinase 1-mediated apoptosis. In summary, our results identified that mammalian sterile 20-like kinase 1 is a novel downstream target of pyruvate kinase M2, and knockdown of pyruvate kinase M2 contributes apoptosis via promoting nuclear translocation of mammalian sterile 20-like kinase 1 by enhancing Caspase-3-dependent cleavage.
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http://dx.doi.org/10.1177/1010428317692251DOI Listing
April 2017

Invalidation of mitophagy by FBP1-mediated repression promotes apoptosis in breast cancer.

Tumour Biol 2017 Jun;39(6):1010428317708779

Key Laboratory of Diagnostic Medicine Designated by the Ministry of Education, Chongqing Medical University, Chongqing, P.R. China.

Fructose-1,6-bisphosphatase 1, a rate-limiting enzyme in gluconeogenesis, was recently shown to be a tumor suppressor. However, the functions of fructose-1,6-bisphosphatase 1 in the regulation of mitophagy and apoptosis remain unknown. Here, we investigated the effects of fructose-1,6-bisphosphatase 1 on mitophagy and apoptosis as well as their underlying mechanisms in breast cancer cells. In this work, the messenger RNA and protein expression of various molecules were determined by quantitative realtime polymerase chain reaction and western blot, respectively. Gene-expression correlations were obtained from The Cancer Genome Atlas Breast Cancer database and analyzed using cBioPortal. The levels of cellular reactive oxygen species and apoptotic index were detected by flow cytometry. The mitochondrial membrane potentials were assessed with a JC-1 fluorescent sensor. Subcellular structures were observed under a transmission electron microscope. The intracellular distribution of translocase of outer membrane 20 was detected by immunofluorescence staining. Protein-protein interactions were analyzed by immunoprecipitation. Our results indicated that fructose-1,6-bisphosphatase 1 expression was negatively correlated with autophagy level in breast cancer. Fructose-1,6-bisphosphatase 1 restrained autophagy activity by increasing the level of p62 and decreasing the levels of LC3 and Beclin 1. Additionally, fructose-1,6-bisphosphatase 1 promoted cell apoptosis by upregulating the levels of intracellular ROS and expression of pro-apoptotic proteins such as cleaved PARP, cleaved Caspase 3, and Bax and downregulating the levels of anti-apoptotic proteins such as PARP, Caspase 3, and Bcl-2. Finally, fructose-1,6-bisphosphatase 1 limited the efficient removal of diseased mitochondria and reduced the messenger RNA and protein expressions of HIF-1α, BNIP3L/NIX, and BNIP3. More importantly, fructose-1,6-bisphosphatase 1 facilitated co-action between Bcl-2 and Beclin 1, which may be important in the mechanism of fructose-1,6-bisphosphatase 1-mediated mitophagy inhibition. In summary, loss of mitophagy by fructose-1,6-bisphosphatase 1-mediated repression promotes apoptosis in breast cancer.
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http://dx.doi.org/10.1177/1010428317708779DOI Listing
June 2017

MiR542-3p Regulates the Epithelial-Mesenchymal Transition by Directly Targeting BMP7 in NRK52e.

Int J Mol Sci 2015 Nov 24;16(11):27945-55. Epub 2015 Nov 24.

The Division of Molecular Nephrology and the Creative Training Center for Undergraduates, The M.O.E. Key Laboratory of Laboratory Medical Diagnostics, the College of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China.

Accumulating evidence demonstrated that miRNAs are highly involved in kidney fibrosis and Epithelial-Eesenchymal Transition (EMT), however, the mechanisms of miRNAs in kidney fibrosis are poorly understood. In this work, we identified that miR542-3p could promote EMT through down-regulating bone morphogenetic protein 7 (BMP7) expression by targeting BMP7 3'UTR. Firstly, real-time PCR results showed that miR542-3p was significantly up-regulated in kidney fibrosis in vitro and in vivo. Moreover, Western blot results demonstrated that miR542-3p may promote EMT in the NRK52e cell line. In addition, we confirmed that BMP7, which played a crucial role in anti-kidney fibrosis and suppressed the progression of EMT, was a target of miR542-3p through Dual-Luciferase reporter assay, as did Western blot analysis. The effects of miR542-3p on regulating EMT could also be suppressed by transiently overexpressing BMP7 in NRK52e cells. Taken together, miR542-3p may be a critical mediator of the induction of EMT via directly targeting BMP7.
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http://dx.doi.org/10.3390/ijms161126075DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4661932PMC
November 2015
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