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LncRNA HEIH Enhances Paclitaxel-Tolerance of Endometrial Cancer Cells via Activation of MAPK Signaling Pathway

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Pathology & Oncology Research

Abstract

This study aimed to investigate the function of lncRNA HEIH on promoting endometrial cancer cells’ tolerance of paclitaxel (PTX). LncRNA HEIH expression was measured by QRT-PCR in endometrial cancer tissues, human healthy tissues and cell lines. The PTX-resistant endometrial cancer cells (Ishikawa-RE and HHUA-RE) were intermittently exposed to increase concentrations of PTX and were constructed as evidenced by MTT assay. Besides, the specific siRNA of HEIH (siHEIH) and pcDNA3.1-HEIH plasmid transfection were utilized to alter the expression of HEIH in the cells and investigate the effects of HEIH on resistance to PTX in endometrial cancer cells. Moreover, MTT, colony formation and apoptosis analysis were taken advantage to evaluate cell viability and proliferation when treated with PTX. Then, differential genes in PTX-resistant and HEIH-knock-down PTX-resistant endometrial cancer cells were screened out by microarray analysis. Finally, gene-set enrichment analysis was used to predict the promising signaling pathway of HEIH and western blotting analysis were performed to verify the relevant genes expression of MAPK signaling pathway. LncRNA HEIH, the dysregulation of which involved in production of drug-resistance, was overexpressed in PTX-resistant endometrial cancer cells. Up-regulating HEIH would activate MAPK pathway, promote chemo-resistance of endometrial cancer cells and enhance cell proliferation and viability, whereas silencing HEIH depressed the MAPK signaling pathway, contributed to restoring chemo-sensitivity to PTX and repressed cell physiological process. Down-regulating lncRNA HEIH expression reversed the PTX-resistance of endometrial cancer cells through MAPK signaling pathway.

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Funding

This study was funded by New Bud Science Foundation(KX104), West China Second University Hospital, Sichuan University.

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Author notes

  1. Jun-Liang Guo and Tian Tang contributed equally to this work.

Authors and Affiliations

  1. Center for Reproductive Medicine, Department of Gynecology and Obstetrics, West China Second University Hospital, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Sichuan University, No.20 Section 3, Renmin South Road, Chengdu City, 610041, Sichuan, People’s Republic of China

    Jun-Liang Guo, Tian Tang, Jin-Hong Li, Yi-Hong Yang, Long Zhang & Yi Quan

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  1. Jun-Liang Guo
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  2. Tian Tang
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  3. Jin-Hong Li
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  4. Yi-Hong Yang
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  5. Long Zhang
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  6. Yi Quan
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Contributions

JG, TT and JL: conception and design, analysis and interpretation of data; YY and LZ: drafting the article; YQ: revising it critically for important intellectual content. YQ is the guarantor.

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Correspondence to Yi Quan.

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Ethical Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the committee of West China Second University Hospital and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This article does not contain any studies with animals performed by any of the authors.

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Informed consent was obtained from all individual participants included in the study.

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The authors declare that they have no conflict of interest.

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Guo, JL., Tang, T., Li, JH. et al. LncRNA HEIH Enhances Paclitaxel-Tolerance of Endometrial Cancer Cells via Activation of MAPK Signaling Pathway. Pathol. Oncol. Res. 26, 1757–1766 (2020). https://doi.org/10.1007/s12253-019-00718-w

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