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LncRNA MALAT1 mediates doxorubicin resistance of hepatocellular carcinoma by regulating miR-3129-5p/Nova1 axis

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Abstract

Drug resistance is one of the major challenges for cancer therapies. In recent years, research on disease-related molecular signaling pathways has become the key ways to understand and overcome obstacles. Dysregulation of MALAT1 could regulate doxorubicin resistance of hepatocellular carcinoma (HCC), but how MALAT1 involving in managing doxorubicin resistance remains unclear yet. We aimed to elucidate the specific molecular mechanism of MALAT1 with doxorubicin resistance in HCC cells. Quantitative real-time polymerase chain reaction (qRT-PCR) was engaged to detect the expression levels of MALAT1, miR-3129-5p and Nova1 mRNA; MTT, western blot, flow cytometry and luciferase reporter assays were executed to identify the influence of MALAT1 on doxorubicin resistance of HCC cells. Xenograft tumor model was created to confirm the biological function of MALAT1 in doxorubicin resistance of HCC cells in vivo. MALAT1 and Nova1 were upregulated, while miR-3129-5p expression was decreased in doxorubicin-resistant HCC tissues and cells. Knockdown of MALAT1 regulated doxorubicin resistance of HCC cells through inhibiting cell proliferation, migration, invasion and promoting apoptosis, but antisense miR-3129-5p released the functional effect of MALAT1 knockdown. Nova1, as a target gene of miR-3129-5p, reversed the results of miR-3129-5p expression and enhanced doxorubicin resistance of HCC cells. Xenograft tumor model suggested that dysregulation of MALAT1 regulated tumor growth and Nova1 to mediate doxorubicin resistance of HCC cells by as a sponge for miR-3129-5p in vivo. Elevation of LncRNA MALAT1 mediated doxorubicin resistance and the progression of HCC via a MALAT1/miR-3129-5p/Nova1 axis. This study would be expected to enrich the understanding of doxorubicin resistance of HCC and provide new ideas for HCC treatment strategies.

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Acknowledgements

We express our gratitude to all authors of the included studies for providing additional information and/or data from their studies.

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  1. Yongxian Cao and Feng Zhang have contribute to this work equally.

Authors and Affiliations

  1. Department of Clinical Laboratory, The Affiliated Hospital of Qingdao University, No. 16, Jiangsu Road, Qingdao, 266003, Shandong, China

    Yongxian Cao & Huazheng Pan

  2. Department of Clinical Laboratory, Rizhao City Hospital of Traditional Chinese Medicine, Rizhao, Shandong, China

    Feng Zhang

  3. Medical College, Yanbian University, Yanji, Jilin, China

    Haotian Wang

  4. Department of Infectious Disease, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China

    Chunhua Bi

  5. Department of Clinical Laboratory, Yantaishan Hospital, Yantai, Shandong, China

    Jinpeng Cui

  6. Department of Clinical Laboratory, Qingdao Municipal Hospital, No. 5, Middle Donghai Road, Qingdao, 266071, Shandong, China

    Fenghai Liu

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  1. Yongxian Cao
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Contributions

YC and FZ conceived and designed the study. HW, CB and JC performed the experiments. YC, FZ and FL analyzed the data; YC, FZ and HP wrote the manuscript. All authors read and approved the final manuscript.

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Correspondence to Fenghai Liu or Huazheng Pan.

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Cao, Y., Zhang, F., Wang, H. et al. LncRNA MALAT1 mediates doxorubicin resistance of hepatocellular carcinoma by regulating miR-3129-5p/Nova1 axis. Mol Cell Biochem 476, 279–292 (2021). https://doi.org/10.1007/s11010-020-03904-6

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