271
MET is a receptor tyrosine kinase, act as a proto-oncogene
and promotes the different stages of pathogenesis of esophageal
adenocarcinoma [ 21 – 29 ]. Therefore, sequence-specific therapeu-
tic intervention of MET with RNAi has been shown impressive
potential in killing esophageal adenocarcinoma cells [ 23 , 27 ].
In this chapter, we describe the RNAi in esophageal adenocar-
cinoma cells using MET shRNA as a model gene. Figure 1 illus-
trates the RNAi-mediated silencing of MET in esophageal
adenocarcinoma cells. In the first step, we knockdown of MET
Table 1
RNAi approaches used in esophageal adenocarcinoma
Target
genes Methods of RNAi Remarks References
RFC3 Plasmid construct
shRNA
RFC3 suppression inhibit EAC cells growth and
proliferation
[ 30 ]
STAT3 siRNA
oligonucleotides
Enhanced apoptosis of EAC cells by blocking
anti-apoptotic survivin and BCL2L1 expression
[ 15 ]
SMAD4 siRNA
oligonucleotides
Knockdown of SMAD4 prevents TGF-β1 induced
EMT and inhibited EMT-associated invasive
behavior of EAC cells
[ 19 ]
mPGES-1 siRNA
oligonucleotides
Silencing of mPGES-1 reduced viability and increased
apoptosis of EAC cells
[ 13 ]
IGFBP2 Plasmid vector
construct
Suppression of IGFBP2 sensitized EAC cells to
cisplatin
[ 12 ]
Akt1/
Gli-1
Lentiviral vector
shRNA
Significantly inhibited the viability of EAC by
inactivating ErbB2-PI3K pathway
[ 16 ]
AGR2 Plasmid construct
shRNA
Reduced the tumor growth notably both in vitro and
in vivo
[ 20 ]
Dkk1 siRNA
oligonucleotides
Dkk1 perturbation-mediated malignant
transformation of Barratt’s esophagus
[ 31 ]
Src Lentiviral vector
shRNA
Silencing of Src sensitize Src-mutant EAC cells to
lapatinib therapy
[ 32 ]
COX7A2 siRNA
oligonucleotides
Knockdown of COX7A2 with sRNA increase the
sensitivity of EAC cells to chemo-agents and
reduced cells growth
[ 33 ]
Gli-1 siRNA
oligonucleotides
Inhibition of Gli-1 in EAC cells increased radio-
sensitivity remarkably by inactivating hedgehog
pathway
[ 34 ]
EAC esophageal adenocarcinoma, RFC3 Replication factor C subunit 3, STAT3 Signal transducer and activator of
transcription 3, SMAD4 SMAD family member 4, mPGES-1 Microsomal prostaglandin E synthase-1, IGFBP2 Insulin-
like growth factor binding protein 2, Akt1 RAC-alpha serine/threonine-protein kinase, Gli-1 Gli family Zinc finger 1,
AGR2 adenocarcinoma-associated antigen 2, Dkk1 Dickkopf-related protein 1, Src Proto-oncogene tyrosine-protein
kinase Src, COX7A2 Cytochrome C oxidase subunit 7A2
RNAi Gene Silencing and Esophageal Adenocarcinoma