Table 3.
Functional studies of candidate genes
| Gene symbol |
Selection strategy |
Cytotoxicity validation in cancer cell lines |
|||
|---|---|---|---|---|---|
|
SNP vs. IC50 |
Integrated analysis |
Both SU86 and MDA231 |
Either THP-1 or BDCM |
||
| SNP Location | P < 10-4 |
SNP vs. Exp P < 10-4 |
(cancer cell lines) | (leukemia cell lines) | |
| Exp vs. IC50 P <10-4 | |||||
|
PIGB
|
Intron/coding/5UTR/3UTR |
Gem |
Gem |
Yes |
NP |
|
C3orf23 |
5UTR/upstream |
Gem |
Gem |
No |
NP |
|
ZADH2
|
|
|
Gem |
Yes |
NP |
|
ARHGEF12 |
|
|
Gem |
No |
NP |
|
DPP7 |
|
|
Gem |
No |
NP |
|
PSME3
|
|
|
Gem |
Yes |
NP |
|
NIPSNAP3B |
Intron/5UTR |
Gem |
|
No |
NP |
|
PIK3R1 |
Flanking_5UTR/3UTR |
Gem |
|
No |
NP |
|
DOK6
|
Intron |
Gem |
|
Yes |
NP |
|
TGFBI
|
Flanking_5UTR |
Gem |
|
Yes |
NP |
|
UNC13C |
|
|
AraC |
No |
No |
|
C14orf169
|
|
|
AraC |
Yes |
NP |
|
MAP4K4 |
|
|
AraC |
No |
NP |
|
URB2 |
Downstream |
AraC |
|
No |
No |
|
TUSC3
|
Intron/5UTR/3UTR |
AraC |
|
Yes |
No |
|
LARS2 |
5UTR |
AraC |
|
Yes |
No |
|
RIS1 (TMEM158)
|
5UTR |
AraC |
|
Yes |
Yes |
|
IGSF4 (CADM1) |
Intron/downstream/3UTR |
AraC |
|
No |
No |
|
LNX2
|
Intron/5UTR/3UTR |
AraC |
|
Yes |
No |
|
SMC2
|
3UTR |
AraC |
|
Yes |
Yes |
|
PLD5 |
Intron |
Both |
|
No |
NP |
|
GPR98 |
Intron |
Both |
|
No |
No |
|
HLA-DRA
|
Intron/3UTR |
Both |
|
Yes |
No |
|
ZNF215 |
Flanking_5UTR/3UTR/coding |
Both |
|
No |
No |
| CABLES1 | Both | No | No | ||
The table lists the top 26 candidate genes selected for siRNA screening for both gemcitabine and AraC, with MTS assay results as well as QRT-PCR assay results when appropriate.
A total of 26 genes were selected for siRNA screening, with 11 genes for gemcitabine, 10 for AraC, and 5 for both. For the validation assays with MTS and QRT-PCR, “Yes” indicates that knockdown of the gene altered drug cytotoxicity, while “No” indicates no alteration. “NP” indicates not performed. The genes that are bolded were functionally validated.