The LncRNA H19/miR‐193a‐3p axis modifies the radio‐resistance and chemotherapeutic tolerance of hepatocellular carcinoma cells by targeting PSEN1

Abstract

This study was designated to verify if the lncRNA H19/miR-193a-3p axis would play a regulatory role in the radio-/chemo-resistances of HCC cells through targeting PSEN1. Within the study, five human HCC cell lines were prepared, including Bel-7402, HepG2, Hep3b, QGY-7703, and SMMC-7721. Moreover, docetaxel (DT), paclitaxel (Pt), vinorelbine (Vb), and 5-fluorouracil (5-Fu) were managed as the chemo-therapeutics, and single-dose X-rays were performed as radio-therapies. Besides, lncRNA H19 and miR-193a-3p were detected by qRT-PCR and Western blot were implemented to quantify the expressional levels of PSEN1, Ku80, γ-H2AX, and RAD51. Luciferase reporter gene assay was advanced to verify the targeted relationship between lncRNA H19 and miR-193a-3p. As a consequence, QGY-7703 and Bel-7402 were, respectively, the most radiation-sensitive and radiation-proof cell lines, and Bel-7402 was associated with the highest resistances to DT, Pt, Vb, and 5-FU. The restrained lncRNA H19 and over-expressed miR-193a-3p expressions tended to significantly elevate the survival rate and proliferation of Bel-7402 cells, when they were exposed to radiation and subject to chemo-therapies. The lncRNA H19 was also found to directly target miR-193a-3p in inducing the HCC development. PSEN1 appeared to be subject to the modification of lncRNA H19 and miR-193a-3p in its acting on the survival rates and proliferative abilities of HCC cells. The lncRNA H19/miR-193a-3p/PSEN1 axis could be regarded as the treatment targets for HCC, so as to further improve the treatment efficacy of chemo- and radio-therapies for HCC.

Presenilin1 exerts antiproliferative effects by repressing the Wnt/β-catenin pathway in glioblastoma

“…On one hand, Ham, S et al reported the inverse correlation of AD and cancer observed in the Presenilin1-KO mouse model of AD [20]. The downregulation of Presenilin1 in hepatocellular carcinoma cells promotes cell survival and decreases cell apoptosis to modify radioresistance and chemotherapeutic tolerance [14]. Similarly, the expression level of Presenilin1 is negatively correlated with bladder cancer chemoresistance [12].…”

“…Moreover, Presenilin1 regulates the paired phosphorylation of β-Catenin independently of Axin/CK-1α in tumorigenesis [9]. Presenilin1 was reported to be involved in ovarian cancer [10], gastric cancer [11], bladder cancer [12], colorectal cancer [13] and hepatocellular carcinoma [14]. However, despite AD being most frequent disease of neurology and glioblastoma being most common tumor of neurosurgery departments, the detailed roles of this AD-related molecule in glioblastoma have not yet been thoroughly validated, and the underlying mechanism needs to be clarified.…”

<p>Knockdown of LINC00473 Enhances Radiosensitivity in Hepatocellular Carcinoma via Regulating the miR-345-5p/FOXP1 Axis</p>

“…24 Additionally, lncRNA H19 triggered the radioresistance of HCC cells by acting as a ceRNA for miR-193a-3p and upregulating PSEN1. 25 Furthermore, knockdown of lncRNA ROR sensitized HCC cells to radiation via regulating the microRNA-145/RAD18 axis. 26 Similar to previous studies, LINC00473 expression was prominently up-regulated in HCC tissues and cells.…”

WITHDRAWN: Mig-6 Promotes the Apoptosis and Inhibits of the Flux of Autophagy in HCC Cell Lines Through Modulating Mig-6/miR-193a-3p/TGF-β2 Axis

“…MiR-193a-3p suppressed ovarian cancer cell growth and migratory/invasive capacities [28]. MiR-193a-3p had also been proven to be related to the migration and invasion [14], proliferation and apoptosis [15,16], radioresistance, and chemotherapeutic tolerance in HCC [29,30]. In addition, the expression of miR-193a-3p was identi ed as a predictor of HCC progression-free survival [31].…”