Kinesin family (KIF) members have vital roles in mitosis, meiosis, and transport of macromolecules in eukaryotic cells. In this study, we aimed to investigate the role of KIF15 in osteosarcoma. Immunohistochemical staining was performed to determine expression levels of KIF15 in osteosarcoma tissues and adjacent normal tissues. Tissue microarray analysis showed a correlation between the expression of KIF15 and pathological features of patients. Subsequently, lentivirus was used to inhibit the expression of KIF15 in osteosarcoma cells. An MTT assay was performed to examine cell proliferation. Transwell and wound healing assays were used to estimate the invasion and migration of osteosarcoma cells, respectively. Flow cytometric analysis was employed to define the apoptosis of osteosarcoma cells. Our results showed that KIF15 expression was significantly upregulated in osteosarcoma tissues compared with adjacent normal tissues. The Mann-Whitney U test and Spearman correlation analysis showed that the expression levels of KIF15 in osteosarcoma tissues were positively correlated with tumor infiltrate, a pathological characteristic of patients. The expression of KIF15 was successfully suppressed by shKIF15, and the knockdown efficiency reached 80 and 69% in MNNG/HOS and U2OS cells, respectively. Subsequently, knockdown of KIF15 significantly inhibited the capacity of cell proliferation, colony formation, invasion, and migration, but enhanced G2 phase arrest and partially enhanced cell apoptosis. This study preliminarily showed KIF15 to be a critical regulatory molecule involved in osteosarcoma cell proliferation. Consequently, KIF15 can be a potential diagnostic and therapeutic target for osteosarcoma.

1.
Moore
DD
,
Luu
HH
.
Osteosarcoma
.
Cancer Treat Res
.
2014
;
162
:
65
92
.
[PubMed]
0927-3042
2.
Botter
SM
,
Neri
D
,
Fuchs
B
.
Recent advances in osteosarcoma
.
Curr Opin Pharmacol
.
2014
Jun
;
16
:
15
23
.
[PubMed]
1471-4892
3.
Ma
W
,
Zhang
X
,
Chai
J
,
Chen
P
,
Ren
P
,
Gong
M
.
Circulating miR-148a is a significant diagnostic and prognostic biomarker for patients with osteosarcoma
.
Tumour Biol
.
2014
Dec
;
35
(
12
):
12467
72
.
[PubMed]
1010-4283
4.
Mori
T
,
Sato
Y
,
Miyamoto
K
,
Kobayashi
T
,
Shimizu
T
,
Kanagawa
H
, et al.
TNFα promotes osteosarcoma progression by maintaining tumor cells in an undifferentiated state
.
Oncogene
.
2014
Aug
;
33
(
33
):
4236
41
.
[PubMed]
0950-9232
5.
Liu
C
,
Zhao
P
,
Yang
Y
,
Xu
X
,
Wang
L
,
Li
B
.
Ampelopsin suppresses TNF-α-induced migration and invasion of U2OS osteosarcoma cells
.
Mol Med Rep
.
2016
Jun
;
13
(
6
):
4729
36
.
[PubMed]
1791-2997
6.
Miki
H
,
Okada
Y
,
Hirokawa
N
.
Analysis of the kinesin superfamily: insights into structure and function
.
Trends Cell Biol
.
2005
Sep
;
15
(
9
):
467
76
.
[PubMed]
0962-8924
7.
Hirokawa
N
.
Kinesin and dynein superfamily proteins and the mechanism of organelle transport
.
Science
.
1998
Jan
;
279
(
5350
):
519
26
.
[PubMed]
0036-8075
8.
Zhu
C
,
Zhao
J
,
Bibikova
M
,
Leverson
JD
,
Bossy-Wetzel
E
,
Fan
JB
, et al.
Functional analysis of human microtubule-based motor proteins, the kinesins and dyneins, in mitosis/cytokinesis using RNA interference
.
Mol Biol Cell
.
2005
Jul
;
16
(
7
):
3187
99
.
[PubMed]
1059-1524
9.
Tan
MH
,
De
S
,
Bebek
G
,
Orloff
MS
,
Wesolowski
R
,
Downs-Kelly
E
, et al.
Specific kinesin expression profiles associated with taxane resistance in basal-like breast cancer
.
Breast Cancer Res Treat
.
2012
Feb
;
131
(
3
):
849
58
.
[PubMed]
0167-6806
10.
Yu
Y
,
Feng
YM
.
The role of kinesin family proteins in tumorigenesis and progression: potential biomarkers and molecular targets for cancer therapy
.
Cancer
.
2010
Nov
;
116
(
22
):
5150
60
.
[PubMed]
0008-543X
11.
Wang
Q
,
Zhao
ZB
,
Wang
G
,
Hui
Z
,
Wang
MH
,
Pan
JF
, et al.
High expression of KIF26B in breast cancer associates with poor prognosis
.
PLoS One
.
2013
Apr
;
8
(
4
):
e61640
.
[PubMed]
1932-6203
12.
Hung
PF
,
Hong
TM
,
Hsu
YC
,
Chen
HY
,
Chang
YL
,
Wu
CT
, et al.
The motor protein KIF14 inhibits tumor growth and cancer metastasis in lung adenocarcinoma
.
PLoS One
.
2013
Apr
;
8
(
4
):
e61664
.
[PubMed]
1932-6203
13.
Wang
Q
,
Wang
L
,
Li
D
,
Deng
J
,
Zhao
Z
,
He
S
, et al.
Kinesin family member 14 is a candidate prognostic marker for outcome of glioma patients
.
Cancer Epidemiol
.
2013
Feb
;
37
(
1
):
79
84
.
[PubMed]
1877-7821
14.
Tanenbaum
ME
,
Macůrek
L
,
Janssen
A
,
Geers
EF
,
Alvarez-Fernández
M
,
Medema
RH
.
Kif15 cooperates with eg5 to promote bipolar spindle assembly
.
Curr Biol
.
2009
Nov
;
19
(
20
):
1703
11
.
[PubMed]
0960-9822
15.
Wang
J
,
Guo
X
,
Xie
C
,
Jiang
J
.
KIF15 promotes pancreatic cancer proliferation via the MEK-ERK signalling pathway
.
Br J Cancer
.
2017
Jul
;
117
(
2
):
245
55
.
[PubMed]
0007-0920
16.
Liu
QZ
,
Gao
XH
,
Chang
WJ
,
Gong
HF
,
Fu
CG
,
Zhang
W
, et al.
Expression of ITGB1 predicts prognosis in colorectal cancer: a large prospective study based on tissue microarray
.
Int J Clin Exp Pathol
.
2015
Oct
;
8
(
10
):
12802
10
.
[PubMed]
1936-2625
17.
Qiao
Y
,
Chen
J
,
Ma
C
,
Liu
Y
,
Li
P
,
Wang
Y
, et al.
Increased KIF15 Expression Predicts a Poor Prognosis in Patients with Lung Adenocarcinoma
.
Cell Physiol Biochem
.
2018
;
51
(
1
):
1
10
.
[PubMed]
1015-8987
18.
PosthumaDeBoer
J
,
Witlox
MA
,
Kaspers
GJ
,
van Royen
BJ
.
Molecular alterations as target for therapy in metastatic osteosarcoma: a review of literature
.
Clin Exp Metastasis
.
2011
Jun
;
28
(
5
):
493
503
.
[PubMed]
0262-0898
19.
Zhou
W
,
Hao
M
,
Du
X
,
Chen
K
,
Wang
G
,
Yang
J
.
Advances in targeted therapy for osteosarcoma
.
Discov Med
.
2014
Jun
;
17
(
96
):
301
7
.
[PubMed]
1944-7930
20.
Lawrence
CJ
,
Dawe
RK
,
Christie
KR
,
Cleveland
DW
,
Dawson
SC
,
Endow
SA
, et al.
A standardized kinesin nomenclature
.
J Cell Biol
.
2004
Oct
;
167
(
1
):
19
22
.
[PubMed]
0021-9525
21.
Wang
W
,
Cao
L
,
Wang
C
,
Gigant
B
,
Knossow
M
.
Kinesin, 30 years later: recent insights from structural studies
.
Protein Sci
.
2015
Jul
;
24
(
7
):
1047
56
.
[PubMed]
0961-8368
22.
Mazumdar
M
,
Sundareshan
S
,
Misteli
T
.
Human chromokinesin KIF4A functions in chromosome condensation and segregation
.
J Cell Biol
.
2004
Aug
;
166
(
5
):
613
20
.
[PubMed]
0021-9525
23.
Castillo
A
,
Morse
HC
 3rd
,
Godfrey
VL
,
Naeem
R
,
Justice
MJ
.
Overexpression of Eg5 causes genomic instability and tumor formation in mice
.
Cancer Res
.
2007
Nov
;
67
(
21
):
10138
47
.
[PubMed]
0008-5472
24.
Nakata
T
,
Hirokawa
N
.
Point mutation of adenosine triphosphate-binding motif generated rigor kinesin that selectively blocks anterograde lysosome membrane transport
.
J Cell Biol
.
1995
Nov
;
131
(
4
):
1039
53
.
[PubMed]
0021-9525
25.
Liu
Z
,
Rebowe
RE
,
Wang
Z
,
Li
Y
,
Wang
Z
,
DePaolo
JS
, et al.
KIF3a promotes proliferation and invasion via Wnt signaling in advanced prostate cancer
.
Mol Cancer Res
.
2014
Apr
;
12
(
4
):
491
503
.
[PubMed]
1541-7786
26.
Venere
M
,
Horbinski
C
,
Crish
JF
,
Jin
X
,
Vasanji
A
,
Major
J
, et al.
The mitotic kinesin KIF11 is a driver of invasion, proliferation, and self-renewal in glioblastoma
.
Sci Transl Med
.
2015
Sep
;
7
(
304
):
304ra143
.
[PubMed]
1946-6234
27.
McHugh
T
,
Drechsler
H
,
McAinsh
AD
,
Carter
NJ
,
Cross
RA
.
Kif15 functions as an active mechanical ratchet.
Mol Biol Cell.
2018
:mbcE18030151.
28.
Eskova
A
,
Knapp
B
,
Matelska
D
,
Reusing
S
,
Arjonen
A
,
Lisauskas
T
, et al.
An RNAi screen identifies KIF15 as a novel regulator of the endocytic trafficking of integrin
.
J Cell Sci
.
2014
Jun
;
127
(
Pt 11
):
2433
47
.
[PubMed]
0021-9533
29.
Zou
JX
,
Duan
Z
,
Wang
J
,
Sokolov
A
,
Xu
J
,
Chen
CZ
, et al.
Kinesin family deregulation coordinated by bromodomain protein ANCCA and histone methyltransferase MLL for breast cancer cell growth, survival, and tamoxifen resistance
.
Mol Cancer Res
.
2014
Apr
;
12
(
4
):
539
49
.
[PubMed]
1541-7786
30.
Chen
J
,
Li
S
,
Zhou
S
,
Cao
S
,
Lou
Y
,
Shen
H
, et al.
Kinesin superfamily protein expression and its association with progression and prognosis in hepatocellular carcinoma
.
J Cancer Res Ther
.
2017
;
13
(
4
):
651
9
.
[PubMed]
0973-1482
31.
Sebastian
J
.
Dihydropyrazole and dihydropyrrole structures based design of Kif15 inhibitors as novel therapeutic agents for cancer
.
Comput Biol Chem
.
2017
Jun
;
68
:
164
74
.
[PubMed]
1476-9271
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.