Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P42574 (caspase-3)
 45,978 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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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PMID:CASC2/miR-24/miR-221 modulates the TRAIL resistance of hepatocellular carcinoma cell through caspase-8/caspase-3. 2947 51

Long non-coding RNAs (LncRNAs) have been shown to be involved in diverse cellular and physiological processes. Recent studies have proved their potential as the prospective therapeutic targets for cancer treatment. Herein, we examined the role of LncRNA CASC2 in human colon cancer. The gene expression analysis showed that LncRNA CASC2 is significantly suppressed in colon cancer tissues and cell lines. The immunohistochemistry also showed considerable increase of the Ki67 in colon cancer tissues suggestive of their aggressiveness. Overexpression of CASC2 inhibited the growth of HT-29 cells. The inhibition of HT-29 growth was due to the induction of apoptosis which was accompanied by upsurge of Bax, depletion of Bcl-2 and activation of caspase-3 cleavage. Electron microscopic analysis showed CASC2 overexpression also induced autophagy in the HT-29 cells which was associated with increase in LC3B II and Beclin 1 expression. Bioinformatic approaches and dual luciferase assay showed that CASC2 controls the TRIM16 via microRNA-214 axis. TRIM16 was found to be overexpressed in all the colon cancer tissues and cell lines. Overexpression of CASC2 caused significant inhibition of TRIM16. Additionally, silencing of TRIM16 resulted in the inhibition of HT-29 cell growth similar to that of CASC2 overexpression. Taken together, CASC2 may prove to be an important therapeutic target for colon cancer treatment.
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PMID:Long non-coding RNA CASC2 induces apoptosis and autophagy in human colon cancer cells via modulation of TRIM16 expression. 3265 1