LncRNA MALAT1 mediates doxorubicin resistance of hepatocellular carcinoma by regulating miR-3129-5p/Nova1 axis
- PDF / 4,265,010 Bytes
- 14 Pages / 595.276 x 790.866 pts Page_size
- 58 Downloads / 167 Views
LncRNA MALAT1 mediates doxorubicin resistance of hepatocellular carcinoma by regulating miR‑3129‑5p/Nova1 axis Yongxian Cao1 · Feng Zhang2 · Haotian Wang3 · Chunhua Bi4 · Jinpeng Cui5 · Fenghai Liu6 · Huazheng Pan1 Received: 19 March 2020 / Accepted: 7 September 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
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. Keywords MALAT1 · miR-3129-5p · Nova1 · Doxorubicin resistance · HCC · Chemotherapy
Introduction The International Agency for Research on Cancer estimated liver cancer became the sixth most common malignant tumor, and the second death-associated tumor for males, Yongxian Cao and Feng Zhang have contribute to this work equally. * Fenghai Liu [email protected] * Huazheng Pan [email protected] 1
Department of Clinical Laboratory, The Affiliated Hospital of Qingdao University, No. 16, Jiangsu Road, Qingdao 266003, Shandong, China
Department of Clinical Laboratory, Rizhao City Hospital of Traditional Chinese Medicine, Rizhao, Shandong, China
2
with about 841,000 new cases and 782,000 deaths annually in 2018 [1]. Primary liver cancer is a high-threat malignant tumor in China and occurs in hepatocytes and intrahepatic bile duct epithelial cells. Hepat
Data Loading...
