Long non-coding RNA HOXA11-AS knockout inhibits proliferation and overcomes drug resistance in ovarian cancer

Abstract

In ovarian carcinogenesis and progression, long non-coding RNAs (lncRNAs) have been shown to have a role, although the underlying processes remain a mystery. By modulating the degree of autophagy in ovarian cancer cells, we sought to learn more about the function lncRNA HOXA11-AS plays in the development of ovarian cancer. The expression of HOXA11-AS in ovarian normal cells and ovarian cancer cell lines was measured using R package and qRT-PCR. Ovarian cancer cells expressed HOXA11-AS substantially higher than normal cells, while cisplatin-resistant cells expressed HOXA11-AS significantly higher than ovarian cancer cells. Next, we studied the prognostic data of HOXA11-AS in ovarian cancer in the Tissue Cancer Genome Atlas (TCGA). In the next step, lentiviral transfection of ovarian cancer cells A2780, OVCAR3, and A2780/DDP (cisplatin-resistant) were performed, and HOXA11-AS knockdown was found to significantly inhibit cell viability, migration, and invasion of A2780 and OVCAR3 cells, and promote apoptosis by CCK-8 assay, transwell assay, cell cycle, and apoptosis assay, and promoted the sensitivity of A2780/DDP cells to cisplatin. It has been shown by the western blot test that HOXA11-AS knockdown increases the amount of cellular autophagy in cells. In contrast, adding the autophagy inhibitor 3-methyladenine (3-MA) to HOXA11-AS cells knocked down in vivo reduced its anti-tumor properties. As a whole, this study found that HOXA11-AS knockdown increased the expression of autophagy-related proteins and improved cisplatin sensitivity, decreased ovarian cancer cell proliferation, and promoted cell apoptosis. This study provides new insights into the role of HOXA11-AS in ovarian cancer regulation.

Development and verification of a 7-lncRNA prognostic model based on tumor immunity for patients with ovarian cancer

“…LINC02207 was also identified as a predictive marker with significant prognostic value in ovarian carcinoma [ 35 ]. Another study found that lncRNA HOXA11.AS knockdown increased the expression of autophagy-related proteins and improved cisplatin sensitivity, decreased ovarian cancer cell proliferation, and promoted cell apoptosis [ 36 ]. As an epithelial-mesenchymal transition (EMT) related lncRNA [ 37 ], researchers found that PMSB8.AS1 promoted pancreatic cancer (PC) progression via STAT1 by sponging miR-382-3p involving regulation PD-L1 [ 38 ].…”

c-Myc-Regulated lncRNA-IGFBP4 Suppresses Autophagy in Cervical Cancer-Originated HeLa Cells

“…It is generally considered a survival mechanism through which cells remove unwanted, misfolded, or aggregated proteins; damaged organelles; and intracellular pathogens [35,36], and autophagic cell death is considered a nonapoptotic cell death [37,38]. Various factors have been identified as a regulator of autophagy including proteins and lncRNAs [33,[39][40][41], such as XIST, MALAT1, HOXA11-AS, and SNHG6, which are the well-known regulators of autophagy [42][43][44][45].…”

Long noncoding RNAs as therapeutic targets to overcome chemoresistance in ovarian cancer

“…Knockdown of lncRNA HOXA11-AS suppressed cell proliferation and overcame cisplatin resistance in ovarian cancer ( Chen et al, 2022c ). Cisplatin-resistance ovarian cancer cells had a higher expression of lncRNA HOXA11-AS compared with normal cells.…”

“…Cisplatin-resistance ovarian cancer cells had a higher expression of lncRNA HOXA11-AS compared with normal cells. Silencing of lncRNA HOXA11-AS in ovarian cancer cells suppressed cell viability, invasion and migration, but promoted apoptosis ( Chen et al, 2022c ). Knockout of lncRNA HOXA11-AS increased cisplatin sensitivity in cisplatin-resistant ovarian cancer cells.…”

“…Knockout of lncRNA HOXA11-AS increased cisplatin sensitivity in cisplatin-resistant ovarian cancer cells. LncRNA HOXA11-AS depletion elevated cellular autophagy in ovarian cancer cells ( Chen et al, 2022c ).…”