Lentivirus-mediated RNA interference targeting the H19 gene inhibits cell proliferation and apoptosis in human choriocarcinoma cell line JAR

Abstract

BackgroundH19 is a paternally imprinted gene that has been shown to be highly expressed in the trophoblast tissue. Results from previous studies have initiated a debate as to whether noncoding RNA H19 acts as a tumor suppressor or as a tumor promotor in trophoblast tissue. In the present study, we developed lentiviral vectors expressing H19-specific small interfering RNA (siRNA) to specifically block the expression of H19 in the human choriocarcinoma cell line JAR. Using this approach, we investigated the impact of the H19 gene on the proliferation, invasion and apoptosis of JAR cells. Moreover, we examined the effect of H19 knockdown on the expression of insulin-like growth factor 2 (IGF2), hairy and enhancer of split homologue-1 (HES-1) and dual-specific phosphatase 5 (DUSP5) genes.ResultsH19 knockdown inhibited apoptosis and proliferation of JAR cells, but had no significant impact on cell invasion. In addition, H19 knockdown resulted in significant upregulation of HES-1 and DUSP5 expression, but not IGF2 expression in JAR cells.ConclusionsThe finding that H19 downregulation could simultaneously inhibit proliferation and apoptosis of JAR cells highlights a putative dual function for H19 in choriocarcinoma and may explain the debate on whether H19 acts as a tumor suppressor or a tumor promotor in trophoblast tissue. Furthermore, upregulation of HES-1 and DUSP5 may mediate H19 downregulation-induced suppression of proliferation and apoptosis of JAR cells.

Long Noncoding RNA H19/miR-675 Axis Promotes Gastric Cancer via FADD/Caspase 8/Caspase 3 Signaling Pathway

“…For instance, it has been shown that H19 can promote gastric cancer and thyroid cancer [21, 22]. On the contrary, Yu et al reported that H19 potentiated choriocarcinoma cell apoptosis [12]. In our study H19 inhibited apoptosis and promoted the proliferation of gastric cancer cells, which is consistent with other recent studies [23-25].…”

“…It has been reported that H19, a 2.3-kb lncRNA which is transcribed from H19/Igf2 gene cluster located on human chromosome 11p15.5, is among the strongly upregulated lncRNAs [9, 10]. Furthermore, H19 has been reported to regulate tumorigenesis in recent years but whether H19 acts as a tumor suppressor or as a tumor promotor is still controversial [11, 12]. In addition, the precise underlying mechanism of its function still remains elusive and needs to be further explored.…”

The long noncoding RNA H19 promotes cell proliferation via E2F-1 in pancreatic ductal adenocarcinoma

“…[10][11][12][13] In contrast, overexpression of H19 has been documented in breast cancer, bladder cancer, gastric cancer, colon cancer, esophageal cancer, lung cancer, osteosarcoma, epithelial ovarian cancer and cervical cancer. 8,[14][15][16][17][18][19][20][21] Aberrant expression of H19 in these tumors is related to increased cell proliferation and invasion and reduced apoptosis.…”

Are breast cancer stem cells the key to resolving clinical issues in breast cancer therapy?

“…Hao et al reported that overexpression of H19 lowered the tumorigenic properties of cells, which demonstrates the tumor suppressor activity of H19 (55). Conversely, several studies have suggested its tumorigenic role in many cancers, including breast cancer (56)(57)(58)(59)(60)(61)(62)(63). A relationship between H19 and cancer stemness has also been suggested.…”