Long noncoding RNA LINC00152 promotes cell proliferation through competitively binding endogenous miR‐125b with MCL‐1 by regulating mitochondrial apoptosis pathways in ovarian cancer

Abstract

Recently, an increasing number of studies have focused on the key function of long noncoding RNAs (lncRNAs) in biological activity. Abnormal lncRNA expression was found to relate to the development and pathogenesis of multiple cancers. LncRNA LINC00152 served as an oncogene in multiple cancers; however, its role in ovarian cancer remains unknown. In our research study, LINC00152 was upregulated in ovarian cancer tissues and cell lines. An increasing LINC00152 level was positively correlated with the histological grade, clinical stage, and poor prognosis of ovarian cancer patients. In addition, knockdown of LINC00152 reduced cell growth, induced cell apoptosis, and suppressed tumor growth. Moreover, we revealed that LINC00152 and Myeloid cell leukemia‐1 (MCL‐1) were targeted by miR‐125b and had the same miR‐125b combining site. The miR‐125b level was negatively correlated with the expression of LINC00152, while MCL‐1 was positively related to the LINC00152 level. MiR‐125b could affect LINC00152 levels as evaluated by qRT‐PCR. Finally, we affirmed that LINC00152 mediated cell proliferation by affecting MCL‐1 expression and MCL‐1‐mediated mitochondrial apoptosis pathways and by working as a competitive endogenous RNA (ceRNA) of miR‐125b. In summary, based on ceRNA theory, the combined research on miR‐125b and MCL‐1, and taking LINC00152 as a new study point, we provide new insight into the molecular mechanism of reversing cell proliferation in ovarian cancer.

SATB1 3′‐UTR and lncRNA‐UCA1 competitively bind to miR‐495‐3p and together regulate the proliferation and invasion of gastric cancer

“…18,19 However, little study has investigated the regulatory effect of mRNA on lncRNA through sponging miRNA. 18,19 However, little study has investigated the regulatory effect of mRNA on lncRNA through sponging miRNA.…”

“…However, growing evidence suggests that lncRNAs and miRNAs play crucial roles in various biological processes but their expression dysregulation is also implicated in regulating or coordinating diverse pathologies (eg, cancer). 18,19 However, the ceRNA hypothesis also provide a possibility that other RNA transcripts may conversely influence the expression or function of lncRNAs through competitively combining with miRNA. [7][8][9][10][11][12] As increased lncRNA-UCA1 is associated with poor overall survival and disease-free survival of GC patients, lncRNA-UCA1 has been suggested as a promising biomarker for the early detection and prognosis prediction.…”

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

“…Notably, it was also identified that LINC00152 knockdown alone had no significant effect on apoptosis and the expression of drug resistance-associated genes (MDR1, MRP1 and GSTπ) in COC1 cells. Contrastingly, the data from the study by Chen et al (12) demonstrated that LINC00152 silencing significantly promoted apoptosis in the ovarian cancer SKOV3 and A2780 cell lines. This result is inconsistent with ours, potentially due to the selection of different cell lines.…”

“…Another previous study suggested that LINC00152 confers oxaliplatin resistance by regulating the expression of miR-193a-3p, and that it may be an independent prognostic factor for colon cancer (26). Notably, a recent study by Chen et al (12) demonstrated that LINC00152 was upregulated in ovarian cancer tissues and cell lines, and that LINC00152 knockdown promoted apoptosis and inhibited tumor growth, suggesting a pro-cancer effect of LINC00152. To the best of our knowledge, in the present study, the sensitization effect of LINC00152 on cisplatin was evaluated for the first time in ovarian cancer cells.…”

“…In addition, knockdown of lncRNA nuclear enriched abundant transcript 1 significantly increased dexamethasone sensitivity in multiple myeloma cell lines (11). lncRNA LINC00152 (LINC00152) has been suggested to have an oncogenic function in various types of cancer, and a previous study revealed that the downregulation of LINC00152 increased the rate of apoptosis and suppressed tumor growth in ovarian cancer by targeting miR-125b (12). However, the role of LINC00152 in the development of ovarian cancer remains unclear, and few studies have evaluated the effect of LINC00152 in chemotherapy-resistant ovarian cancer.…”