Page 163 - D. Cancer biology

NSMF promotes colorectal cancer growth via the protection

of replication stress
1
1
Kyeong Jin Shin , Yu Jin Lee , Hongtae Kim , Young Chan Chae 1*
1
1 Department of Life Sciences, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, Korea
BACKGROUND AIM
Genomic instability is the consequence of DNA lesions that can result We try to elucidate whether NSMF support viability of cancer cell
from errors in DNA replication, the genotoxic compounds or ultraviolet that breach the tumorigenic barrier by oncogene-induced
and ionizing radiation. Exogenous and endogenous agent can cause replication stress in the colorectal cancer.
DNA damage, followed by activation of the DNA damage checkpoint
and repair pathways, known as DNA damage response (DDR). Several Hypothetical model
DDR-related protein act as tumor suppressor which provide a barrier to
delay or prevent tumorigenesis through the induction of apoptosis or the
establishment of the sustained arrested cell state of senescence.
Otherwise, constitutive DDR activation is observed in cancer for
survival. NSMF (NMDA receptor synaptonuclear signaling and neuronal
migration factor) was identified by differential screen of primary
luteinizing hormone-releasing hormone neurons which migrating or non-
migrating cell. encodes a transcription cofactor with zinc finger domain.
The expression of NSMF was greatest in the brain, but also in the heart,
liver, kidney, and spleen. Interestingly, NSMF could reduced the number
of myoblast cell by inducing apoptotic cell death. According to BioGPS,
NSMF was highly expressed in colorectal adenocarcinomas despite
rarely expression in normal colon tissues. However, whether NSMF is
involved in colorectal cancer development/ growth, and how it may do
so, remains unknown.

RESULTS

Figure 1. Overexpression of NSMF was associated with shorter overall survival Figure 3. Loss of NSMF leads to replication stress-induced senescence
times for colorectal cancer
A 2 4 B 1 0 0 L o w e xp re ssio n (n = 2 1 9 ) A B
N S M F e xp re ssio n (lo g 2 [fp km -u q + 1 ]) 2 2 O v e ra ll S u rv iv a l (% ) 8 0
H ig h e xp re ssio n (n = 2 1 9 )

2 0
6 0
1 8
4 0
1 6
H R = 0 .5 9 0 5 (0 .3 9 9 7 - 0 .8 8 2 8 )
1 4
N o rm a l
T u m o r
1 0 0 0 2 0 0 0 3 0 0 0 4 0 0 0 5 0 0 0
(n = 4 1 ) (n = 4 7 1 ) 2 0 0 0 L o g ra n k P = 0 .0 1 0 1
D a y s
Figure 2. siRNA targeting NSMF inhibited cancer cell proliferation Figure 4. Attenuation of APC-mediated intestinal tumorigenesis in Nsmf knock-out
mice.
A B A B 1 0
200
siCtrl 8
siNSMF-1
Cell number (x10 4 ) 100 siNSMF-2 T u m o r n u m b e r/m o u s e 6 4 *
150
50
0 2 0
1 2 3 4 5 +/+ - /-
N S M F N S M F
CONCLUSION REFERENCES ACKNOWLEDGEMENTS

The current study focused on the elucidation of the role 1. In Vitro Cell Dev Biol Anim. (2015) This work was supported by the National Research
of NSMF in colorectal cancer growth. We check the 51(1):79-84. Foundation of Korea funded by the Ministry of
effect of NSMF on cancer cell growth in-vitro and in-vivo. Science and ICT (2018R1A2B2003129,
Also, the growth inhibition due to G2/M arrest in NSMF- 2. Medchemcomm. (2016). 8(2):295-319 2018R1A5A1024340, 2020R1A2C1011284)
deficient cell was confirmed as a result of defect of 3. Mol Cancer Res. (2007) 5(12):1296-303.
replication stress response (RSR). Abnormal RSR/DDR
pathway is known as one of the causes of cancer 4. Rare Dis. (2016) 4(1):e1241361
therapeutic resistance. Therefore, NSMF may also be 5. Genes Dev. (2011) 25(5):409-33 Contact information
involved in drug resistance, and conversely, NSMF
inhibition may be expected to produce synergistic 6. Nat Rev Cancer. (2015) 15(5):276-89
therapeutic effects. Taken together, NSMF may be key skjin0331@unist.ac.kr
regulator of RSR, and be overexpressed in colorectal
cancer to overcome RS-induced barriers. ychae@unist.ac.kr