MiR-489-3p Reduced Pancreatic Cancer Proliferation and Metastasis By Targeting PKM2 and LDHA Involving Glycolysis

IntroductionMalignant proliferation and metastasis are some of the causes of high mortality in pancreatic cancer. MicroRNAs have been a hot spot in cancer research and are involved in tumor formation and metabolic stress responses. However, the biology function and underlying mechanism of miRNA regu...

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Autores principales: Dan Zhang, Zhiwei He, Yiyi Shen, Jie Wang, Tao Liu, Jianxin Jiang
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Publicado: Frontiers Media S.A. 2021
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Acceso en línea:https://doaj.org/article/bf7e9856b3f74aa89995072acc8c74e6
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spelling oai:doaj.org-article:bf7e9856b3f74aa89995072acc8c74e62021-11-12T04:47:06ZMiR-489-3p Reduced Pancreatic Cancer Proliferation and Metastasis By Targeting PKM2 and LDHA Involving Glycolysis2234-943X10.3389/fonc.2021.651535https://doaj.org/article/bf7e9856b3f74aa89995072acc8c74e62021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fonc.2021.651535/fullhttps://doaj.org/toc/2234-943XIntroductionMalignant proliferation and metastasis are some of the causes of high mortality in pancreatic cancer. MicroRNAs have been a hot spot in cancer research and are involved in tumor formation and metabolic stress responses. However, the biology function and underlying mechanism of miRNA regulating pancreatic cancer progress is remained uncleared.MethodsRNA-seq analysis the glycolysis associated miRNAs and verified miRNA-489-3p was involving in glycolysis. We used RNA in situ hybridization (ISH) and qRT-PCR to analyze the differential expression of miR-489-3p in pancreatic cancer tissues and adjacent tissues and cell lines. Then the function assay of in vivo and in vitro were used to evaluated the role of miR-489-3p in the proliferation, metastasis and glucose metabolism of pancreatic cancer. Furthermore, dual luciferase reporter and rescue experiments were performed to explore the mechanism underlying in the role of miRNA-489-3p.ResultsWe determined that glycolysis associated miRNA miR-489-3p was downregulated in pancreatic cancer tissues and cell lines. The gain and loos of function experiments confirmed that miR-489-3p could inhibit the proliferation, metastasis and glucose metabolism of pancreatic cancer. Further, we found that miR-489-3p could target regulating LDHA and PKM through the luciferase report experiment. Finally, in vivo experiment confirmed that highly expressed miR-489-3p inhibited the growth of pancreatic cancer.ConclusionIn short, this study identified miR-489-3p as a novel therapy target for pancreatic cancer which was involving in the proliferation, metastasis and glycolysis, but its diagnostic value deserves further study.Dan ZhangZhiwei HeYiyi ShenJie WangTao LiuJianxin JiangFrontiers Media S.A.articlemiR-489-3pproliferationglycolysispancreatic cancermetastasisNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENFrontiers in Oncology, Vol 11 (2021)
institution DOAJ
collection DOAJ
language EN
topic miR-489-3p
proliferation
glycolysis
pancreatic cancer
metastasis
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
spellingShingle miR-489-3p
proliferation
glycolysis
pancreatic cancer
metastasis
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
Dan Zhang
Zhiwei He
Yiyi Shen
Jie Wang
Tao Liu
Jianxin Jiang
MiR-489-3p Reduced Pancreatic Cancer Proliferation and Metastasis By Targeting PKM2 and LDHA Involving Glycolysis
description IntroductionMalignant proliferation and metastasis are some of the causes of high mortality in pancreatic cancer. MicroRNAs have been a hot spot in cancer research and are involved in tumor formation and metabolic stress responses. However, the biology function and underlying mechanism of miRNA regulating pancreatic cancer progress is remained uncleared.MethodsRNA-seq analysis the glycolysis associated miRNAs and verified miRNA-489-3p was involving in glycolysis. We used RNA in situ hybridization (ISH) and qRT-PCR to analyze the differential expression of miR-489-3p in pancreatic cancer tissues and adjacent tissues and cell lines. Then the function assay of in vivo and in vitro were used to evaluated the role of miR-489-3p in the proliferation, metastasis and glucose metabolism of pancreatic cancer. Furthermore, dual luciferase reporter and rescue experiments were performed to explore the mechanism underlying in the role of miRNA-489-3p.ResultsWe determined that glycolysis associated miRNA miR-489-3p was downregulated in pancreatic cancer tissues and cell lines. The gain and loos of function experiments confirmed that miR-489-3p could inhibit the proliferation, metastasis and glucose metabolism of pancreatic cancer. Further, we found that miR-489-3p could target regulating LDHA and PKM through the luciferase report experiment. Finally, in vivo experiment confirmed that highly expressed miR-489-3p inhibited the growth of pancreatic cancer.ConclusionIn short, this study identified miR-489-3p as a novel therapy target for pancreatic cancer which was involving in the proliferation, metastasis and glycolysis, but its diagnostic value deserves further study.
format article
author Dan Zhang
Zhiwei He
Yiyi Shen
Jie Wang
Tao Liu
Jianxin Jiang
author_facet Dan Zhang
Zhiwei He
Yiyi Shen
Jie Wang
Tao Liu
Jianxin Jiang
author_sort Dan Zhang
title MiR-489-3p Reduced Pancreatic Cancer Proliferation and Metastasis By Targeting PKM2 and LDHA Involving Glycolysis
title_short MiR-489-3p Reduced Pancreatic Cancer Proliferation and Metastasis By Targeting PKM2 and LDHA Involving Glycolysis
title_full MiR-489-3p Reduced Pancreatic Cancer Proliferation and Metastasis By Targeting PKM2 and LDHA Involving Glycolysis
title_fullStr MiR-489-3p Reduced Pancreatic Cancer Proliferation and Metastasis By Targeting PKM2 and LDHA Involving Glycolysis
title_full_unstemmed MiR-489-3p Reduced Pancreatic Cancer Proliferation and Metastasis By Targeting PKM2 and LDHA Involving Glycolysis
title_sort mir-489-3p reduced pancreatic cancer proliferation and metastasis by targeting pkm2 and ldha involving glycolysis
publisher Frontiers Media S.A.
publishDate 2021
url https://doaj.org/article/bf7e9856b3f74aa89995072acc8c74e6
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