<p>LncRNA HEIH Confers Cell Sorafenib Resistance in Hepatocellular Carcinoma by Regulating miR-98-5p/PI3K/AKT Pathway</p>

Abstract

Background The hepatocellular carcinoma up-regulated EZH2-associated long non-coding RNA (HEIH) has been identified to act as an oncogene to promote cell tumorigenesis in hepatocellular carcinoma (HCC); however, the roles of HEIH in sorafenib resistance in HCC cells remain elusive. Materials and Methods The expression of HEIH and microRNA (miR)-98-5p was detected using quantitative real-time polymerase chain reaction. Cell viability, apoptosis, migration and invasion were analyzed using cell counting kit-8 assay, flow cytometry and transwell assay. Western blot was used to measure the levels of apoptosis-related protein and phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway-related protein. The interaction between HEIH and miR-98-5p was confirmed by dual-luciferase reporter and RNA immunoprecipitation assay. In vivo experiments were performed using murine xenograft models. Results HEIH was up-regulated in sorafenib-resistant HCC tissues and cell lines, and HEIH silence weakened sorafenib resistance by suppressing cell viability, invasion and migration, decreasing the IC 50 values to sorafenib, and increasing apoptosis in sorafenib-resistant HCC cells in vitro and reinforced the anti-tumor effects of sorafenib in vivo. HEIH was a sponge of miR-98-5p, and miR-98-5p inhibition reversed the sorafenib sensitivity induced by HEIH deletion in sorafenib-resistant HCC cells. MiR-98-5p inhibition could activate PI3K/AKT pathway, and enhanced sorafenib resistance by regulating the activation of PI3K/AKT pathway in sorafenib-resistant HCC cells. Besides, HEIH also activated PI3K/AKT pathway through regulating miR-98-5p in sorafenib-resistant HCC cells. Conclusion HEIH conferred an advantage to sorafenib resistance in HCC by the activation of PI3K/AKT pathway through miR-98-5p, indicating a potential therapeutic strategy for HCC chemotherapy.

miR-98-5p plays a critical role in depression and antidepressant effect of ketamine

“…Second, the downstream mechanisms of miR-98-5p in the pathology of depression and antidepressant effects of ketamine are also unclear. Since miR-98-5p has previously been reported to regulate PI3K/Akt signaling pathway [ 28 ], which is significantly involved in depression [ 29 ], and the involvement of PI3K/Akt in the antidepressant effect of ketamine has also been reported [ 30 ], we speculate that ketamine-induced upregulation of miR-98-5p may elicit the antidepressant effect through regulating PI3K/Akt pathway. To explore that possibility, we will investigate the role of PI3K/Akt pathway in the antidepressant effect of ketamine-induced miR-98-5p upregulation in our future work.…”

Long Noncoding RNA MIR100HG Knockdown Attenuates Hepatocellular Carcinoma Progression by Regulating MicroRNA-146b-5p/Chromobox 6

“…In addition, sorafenib, an oral kinase inhibitor, has been confirmed to be a gold quality standard to enhance survival in patients affected by advanced HCC in the first-line treatment [ 31 ]. Interestingly, numerous lncRNAs are overexpressed in HCC tissues and are closely associated with sorafenib resistance, such as SNHG1 [ 32 ], SNHG3 [ 33 ], HEIH [ 34 ], and NEAT1 [ 35 ]. We speculated that the high expression level of MIR100HG may also promote sorafenib resistance to affect the progression of HCC when sorafenib is administered in clinical practice.…”

Circulating Long and Circular Noncoding RNA as Non-Invasive Diagnostic Tools of Hepatocellular Carcinoma

“…Interestingly, the ratio of lncRNA-HEIH expression in serum versus exosomes was decreased compared to patients with chronic hepatitis [ 122 ]. In in vitro model, HEIH is involved in HCC cell growth and metastasis through the regulation of several miRNAs, such as miR-199a-3p and miR-98-5p, and the deactivation of AKT and mTOR pathways [ 123 , 124 , 125 ].…”