<p>Carboplatin Inhibits the Progression of Retinoblastoma Through IncRNA XIST/miR-200a-3p/NRP1 Axis</p>

Abstract

Objective: This study was set out to explore the expression and related mechanism of XIST and miR-200a-3p in retinoblastoma (Rb). Patients and Methods: Fifty-four children with Rb who came to our hospital for surgery from January 2018 to September 2019 were collected. In addition, Rb cells and human retinal epithelial cells were purchased. XIST-siRNA (si-XIST), XIST-shRNA (sh-XIST), empty vector plasmid (siRNA-NC), miR-200a-3p-mimics and miR −200a-3p-inhibition were transfected into Y79 cells. The expression of XIST and miR-200a-3p in the samples were determined by qRT-PCR. β-catenin, cyclin B1, cyclin D1, Bax, Caspase-3, N-cadherin, vimentin, Snail, E-Cadherin and ZO-1 protein levels were measured by WB. MTT, Transwell and flow cytometry were utilized to detect cell proliferation, invasion, and apoptosis, respectively. Results: XIST was highly expressed while miR-200a-3p was lowly expressed in patients' tissues, and the AUC of both was over 0.8. XIST and miR-200a-3p was related to differentiation degree in Rb patients. Y79 cells were selected for transfection. Compared with the siRNA-NC group, XIST was significantly reduced in the siRNA-XIST group, and it was significantly increased in the shRNA-XIST group (P<0.01). The proliferation capacity of siRNA-XIST group was decreased, while that of shRNA-XIST group was up-regulated. The apoptosis rate of siRNA-XIST group was significantly up-regulated, while that of shRNA-XIST group was decreased (P<0.001). The invasive capacity of siRNA-XIST group was decreased, while that of shRNA-XIST group was up-regulated (P<0.001). Silencing XIST and over-expressed miR-200a-3p could inhibit cell epithelial-mesenchymal transition (EMT), proliferation, invasion, and promote apoptosis. WB detection showed that Carboplatin + LncRNA XIST intervention group could more significantly inhibit β-catenin, cyclin B1, cyclin D1, N-cadherin, vimentin, Snail protein, and promote the up-regulation of Bax, Caspase-3, E-Cadherin and ZO-1 expression. Conclusion: Inhibition of XIST expression can up-regulate miR-200a-3p-mediated PI3K-Akt/MAPK-ERK signaling pathway and affect cell EMT, proliferation, invasion, and apoptosis, which is expected to be a potential therapeutic target for Rb.

The crosstalk network of XIST/miR‐424‐5p/OGT mediates RAF1 glycosylation and participates in the progression of liver cancer

“…Similarly, deleting of XIST expression can improve the levels of E‐cadherin 27 . Carboplatin + LncRNA XIST intervention group can suppress the expression of β‐catenin and N‐cadherin 28 . Moreover, overexpressing miR‐7 inhibited lncRNA XIST, reducing the expression of epithelium‐specific antigen by increasing miR‐92b and inhibiting Slug 29 …”

“…27 Carboplatin + LncRNA XIST intervention group can suppress the expression of β-catenin and N-cadherin. 28 Moreover, overexpressing miR-7 inhibited lncRNA XIST, reducing the expression of epithelium-specific antigen by increasing miR-92b and inhibiting Slug. 29 Then, we identified miR-424-5p as a XIST target by intersecting the miRNome data obtained from two HCCs and two control livers with potential XIST miRNA targets retrieved from the RNA22 database.…”

Long non-coding RNA XIST: a novel oncogene in multiple cancers

“…Also, XIST silencing increases the PI3K-Akt/MAPK-ERK axis mediated by miR-200a-3p, which affects cell growth, invasion, apoptosis, and EMT in RBs (Fig. 4 K) (Zhao et al 2020 ). Subsequent studies showed that XIST enhanced the aggressive phenotype of RB cells through miR-361-3p/STX17 signals, functioning as an oncogenic lncRNA (Fig.…”

Biological Function of Long Non-coding RNA (LncRNA) Xist

“…LncRNA Xist overexpression promotes retinoblastoma cells proliferation, migration, and invasion rates via negatively regulating lncRNA NKILA, but the causality has not been fully validated. In addition, lncRNA Xist, which indirectly interacts with miR-21-5p, miR-124, miR-101, miR-140-5p, and miR-200a-3p, and positively regulates VEGF, STAT3, ZEB1 and ZEB2, SOX4, and NRP1 expression, facilitates apoptosis, migration, EMT, proliferation, and invasion by activating signaling pathways, such as PI3K-Akt signaling pathway and MAPK-ERK signaling pathway ( Hu et al, 2018 ; Cheng Y. et al, 2019 ; Dong et al, 2020 ; Wang et al, 2020c ; Zhao H. et al, 2020 ). All in all, these studies suggested that lncRNA Xist serves a potential and promising clinical application for diagnosis, prognosis, and treatment.…”