Kinesin superfamily protein 21B acts as an oncogene in non-small cell lung cancer

Abstract Background Kinesin superfamily proteins (KIFs) serve as microtubule-dependent molecular motors, and are involved in the progression of many malignant tumors. In this study, we aimed to investigate the expression pattern and precise role of kinesin family member 21B (KIF21B) in non-small cel...

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Main Authors: Zhi-Gang Sun, Feng Pan, Jing-Bo Shao, Qian-Qian Yan, Lu Lu, Nan Zhang
Format: Article
Language:English
Published: BMC 2020-06-01
Series:Cancer Cell International
Subjects:
Online Access:http://link.springer.com/article/10.1186/s12935-020-01323-7
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author Zhi-Gang Sun
Feng Pan
Jing-Bo Shao
Qian-Qian Yan
Lu Lu
Nan Zhang
author_facet Zhi-Gang Sun
Feng Pan
Jing-Bo Shao
Qian-Qian Yan
Lu Lu
Nan Zhang
author_sort Zhi-Gang Sun
collection DOAJ
description Abstract Background Kinesin superfamily proteins (KIFs) serve as microtubule-dependent molecular motors, and are involved in the progression of many malignant tumors. In this study, we aimed to investigate the expression pattern and precise role of kinesin family member 21B (KIF21B) in non-small cell lung cancer (NSCLC). Methods KIF21B expression in 72 cases of NSCLC tissues was measured by immunohistochemical staining (IHC). We used shRNA-KIF21B interference to silence KIF21B in NSCLC H1299 and A549 cells and normal lung epithelial bronchus BEAS-2B cells. The biological roles of KIF21B in the growth and metastasis abilities of NSCLC cells were measured by Cell Counting Kit-8 (CCK8), colony formation and Hoechst 33342/PI, wound-healing, and Transwell assays, respectively. Expression of apoptosis-related proteins was determined using western blot. The effect of KIF21B on tumor growth in vivo was examined using nude mice model. Results KIF21B was up-regulated in NSCLC tissues, and correlated with pathological lymph node and pTNM stage, its high expression was predicted a poor prognosis of patients with NSCLC. Silencing of KIF21B mediated by lentivirus-delivered shRNA significantly inhibited the proliferation ability of H1299 and A549 cells. KIF21B knockdown increased apoptosis in H1299 and A549 cells, down-regulated the expression of Bcl-2 and up-regulated the expression of Bax and active Caspase 3. Moreover, KIF21B knockdown decreased the level of phosphorylated form of Akt (p-Akt) and Cyclin D1 expression in H1299 and A549 cells. In addition, silencing of KIF21B impeded the migration and invasion of H1299 and A549 cells. Further, silencing of KIF 21B dramatically inhibited xenograft growth in BALB/c nude mice. However, silencing of KIF21B did not affect the proliferation, migration and invasion of BEAS-2B cells. Conclusions These results reveal that KIF21B is up-regulated in NSCLC and acts as an oncogene in the growth and metastasis of NSCLC, which may function as a potential therapeutic target and a prognostic biomarker for NSCLC.
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spelling doaj.art-356a750cb8244a849af147c1cd2c92aa2022-12-21T16:58:34ZengBMCCancer Cell International1475-28672020-06-0120111210.1186/s12935-020-01323-7Kinesin superfamily protein 21B acts as an oncogene in non-small cell lung cancerZhi-Gang Sun0Feng Pan1Jing-Bo Shao2Qian-Qian Yan3Lu Lu4Nan Zhang5Department of Thoracic Surgery, Central Hospital Affiliated to Shandong First Medical UniversityDepartment of Ethics Committee, Central Hospital Affiliated to Shandong UniversityWeifang Medical UniversityDepartment of Oncology, Jinan Central Hospital, Cheeloo College of Medicine, Shandong UniversityShandong First Medical UniversityDepartment of Oncology, Central Hospital Affiliated to Shandong First Medical UniversityAbstract Background Kinesin superfamily proteins (KIFs) serve as microtubule-dependent molecular motors, and are involved in the progression of many malignant tumors. In this study, we aimed to investigate the expression pattern and precise role of kinesin family member 21B (KIF21B) in non-small cell lung cancer (NSCLC). Methods KIF21B expression in 72 cases of NSCLC tissues was measured by immunohistochemical staining (IHC). We used shRNA-KIF21B interference to silence KIF21B in NSCLC H1299 and A549 cells and normal lung epithelial bronchus BEAS-2B cells. The biological roles of KIF21B in the growth and metastasis abilities of NSCLC cells were measured by Cell Counting Kit-8 (CCK8), colony formation and Hoechst 33342/PI, wound-healing, and Transwell assays, respectively. Expression of apoptosis-related proteins was determined using western blot. The effect of KIF21B on tumor growth in vivo was examined using nude mice model. Results KIF21B was up-regulated in NSCLC tissues, and correlated with pathological lymph node and pTNM stage, its high expression was predicted a poor prognosis of patients with NSCLC. Silencing of KIF21B mediated by lentivirus-delivered shRNA significantly inhibited the proliferation ability of H1299 and A549 cells. KIF21B knockdown increased apoptosis in H1299 and A549 cells, down-regulated the expression of Bcl-2 and up-regulated the expression of Bax and active Caspase 3. Moreover, KIF21B knockdown decreased the level of phosphorylated form of Akt (p-Akt) and Cyclin D1 expression in H1299 and A549 cells. In addition, silencing of KIF21B impeded the migration and invasion of H1299 and A549 cells. Further, silencing of KIF 21B dramatically inhibited xenograft growth in BALB/c nude mice. However, silencing of KIF21B did not affect the proliferation, migration and invasion of BEAS-2B cells. Conclusions These results reveal that KIF21B is up-regulated in NSCLC and acts as an oncogene in the growth and metastasis of NSCLC, which may function as a potential therapeutic target and a prognostic biomarker for NSCLC.http://link.springer.com/article/10.1186/s12935-020-01323-7Non-small cell lung cancerKIF21BProliferationOncogene
spellingShingle Zhi-Gang Sun
Feng Pan
Jing-Bo Shao
Qian-Qian Yan
Lu Lu
Nan Zhang
Kinesin superfamily protein 21B acts as an oncogene in non-small cell lung cancer
Cancer Cell International
Non-small cell lung cancer
KIF21B
Proliferation
Oncogene
title Kinesin superfamily protein 21B acts as an oncogene in non-small cell lung cancer
title_full Kinesin superfamily protein 21B acts as an oncogene in non-small cell lung cancer
title_fullStr Kinesin superfamily protein 21B acts as an oncogene in non-small cell lung cancer
title_full_unstemmed Kinesin superfamily protein 21B acts as an oncogene in non-small cell lung cancer
title_short Kinesin superfamily protein 21B acts as an oncogene in non-small cell lung cancer
title_sort kinesin superfamily protein 21b acts as an oncogene in non small cell lung cancer
topic Non-small cell lung cancer
KIF21B
Proliferation
Oncogene
url http://link.springer.com/article/10.1186/s12935-020-01323-7
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