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2018 ; 9
(3
): 318
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CASC2/miR-24/miR-221 modulates the TRAIL resistance of hepatocellular carcinoma
cell through caspase-8/caspase-3
#MMPMID29476051
Jin X
; Cai L
; Wang C
; Deng X
; Yi S
; Lei Z
; Xiao Q
; Xu H
; Luo H
; Sun J
Cell Death Dis
2018[Feb]; 9
(3
): 318
PMID29476051
show ga
Hepatocellular carcinoma is one of the most common solid tumors in the digestive
system. The prognosis of patients with hepatocellular carcinoma is still poor due
to the acquisition of multi-drug resistance. TNF Related Apoptosis Inducing
Ligand (TRAIL), an attractive anticancer agent, exerts its effect of selectively
inducing apoptosis in tumor cells through death receptors and the formation of
the downstream death-inducing signaling complex, which activates apical caspases
3/8 and leads to apoptosis. However, hepatocellular carcinoma cells are resistant
to TRAIL. Non-coding RNAs, including long non-coding RNAs (lncRNAs) and miRNAs
have been regarded as major regulators of normal development and diseases,
including cancers. Moreover, lncRNAs and miRNAs have been reported to be
associated with multi-drug resistance. In the present study, we investigated the
mechanism by which TRAIL resistance of hepatocellular carcinoma is affected from
the view of non-coding RNA regulation. We selected and validated candidate
miRNAs, miR-24 and miR-221, that regulated caspase 3/8 expression through direct
targeting, and thereby affecting TRAIL-induced tumor cell apoptosis TRAIL
resistance of hepatocellular carcinoma. In addition, we revealed that CASC2, a
well-established tumor suppressive long non-coding RNA, could serve as a "Sponge"
of miR-24 and miR-221, thus modulating TRAIL-induced tumor cell apoptosis TRAIL
resistance of hepatocellular carcinoma. Taken together, we demonstrated a
CASC2/miR-24/miR-221 axis, which can affect the TRAIL resistance of
hepatocellular carcinoma through regulating caspase 3/8; through acting as a
"Sponge" of miR-24 and miR-221, CASC2 may contribute to improving hepatocellular
carcinoma TRAIL resistance, and finally promoting the treatment efficiency of
TRAIL-based therapies.
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