Long non-coding RNA Linc00312 modulates the sensitivity of ovarian cancer to cisplatin <i>via</i> the Bcl-2/Caspase-3 signaling pathway

Abstract

Chemotherapy is one of the main treatments for ovarian cancer (OC). Cisplatin combined with paclitaxel is a commonly used chemotherapy regimen. However, effective cancer therapy is hindered by a patient's resistance to cisplatin. The mechanism that potentially leads to that resistance is unclear. The current study examined the mechanism by which Linc00312 is involved in resistance to cisplatin in OC. Quantitative real-time PCR (RT-qPCR) was used to test for expression of Linc00312 in freshly frozen tissue samples of OC and in SKOV3 and SKOV3/DDP cells. In situ hybridization was performed to examine the distribution of Linc00312 expression in paraffin-embedded histological sections that were sensitive or resistant to cisplatin. The cell counting kit-8 assay was used to detect cell viability. Flow cytometry was used to measure cell apoptosis. RT-qPCR was performed to confirm changes in expression of MDR1, MRP1, Bcl-2, Bax, Caspase-3, and Caspase-9 mRNA. Levels of MDR1, Bcl-2, Bax, Caspase-3, and Caspase-9 protein were detected with Western blotting. Experiments indicated that the expression of Linc00312 decreased significantly in SKOV3/DDP cells compared to that in SKOV3 cells. Upregulation of Linc00312 can considerably increase the sensitivity of SKOV3/DDP cells to cisplatin, while down-regulation of Linc00312 has the exact opposite effect in SKOV3 cells. Linc00312 enhanced the sensitivity of SKOV3/DDP cells to cisplatin by promoting cell apoptosis via the Bcl-2/Caspase-3 signaling pathway. These findings suggest that Linc00312 may be a promising clinical strategy for the treatment of drug-resistant OC.

<p>LncRNA MALAT1 Regulates the Progression and Cisplatin Resistance of Ovarian Cancer Cells via Modulating miR-1271-5p/E2F5 Axis</p>

“…For example, Long et al confirmed that lncRNA GAS5 increased DDP-resistance and promoted OC cell growth through modulating MAPK pathway. 25 Miao et al reported that lncRNA ANRIL changed the sensitivity of OC cells to DDP by mediating let-7a and HMGA2 levels. 26 LncRNA linc00312 regulated DDP resistance of OC cells via modulating Bcl-2/Caspase-3 pathway.…”

Knockdown of long non‑coding RNA LINC00152 increases cisplatin sensitivity in ovarian cancer cells

“…Wang et al (24) demonstrated that the downregulation of Hox transcript antisense intergenic RNA significantly decreased the levels of cell proliferation and invasion, and reversed cisplatin resistance in SKOV-3CDDP/R cells. In addition, Zhang et al (25) indicated that Linc00312 promoted apoptosis and enhanced cisplatin sensitivity through the Bcl-2/Caspase-3 pathway in SKOV3/DDP cells. These studies indicated that lncRNAs have great potential in the treatment of cisplatin resistance.…”

Back to the Future: Rethinking the Great Potential of lncRNAS for Optimizing Chemotherapeutic Response in Ovarian Cancer

“…Various lncRNAs regulate the emergence of chemoresistance via modulating apoptosis. For instance, LINC00312 was shown to counteract PTX resistance in OC and enhance apoptosis via blocking BCL-2 and activating the Bax/Caspas3 apoptotic pathway [ 140 ]. Another lncRNA, CDKN2B-AS, also called antisense ncRNA in the INK4 locus (ANRIL), is overexpressed in a wide array of solid tumors such as hepatocellular carcinoma [ 153 ] and cervical [ 154 ], breast [ 155 ], endometrial, and prostate cancers [ 156 ].…”