Ranran Tang

LINC00629, a HOXB4‐downregulated long noncoding RNA, inhibits glycolysis and ovarian cancer progression by destabilizing c‐Myc

AbstractOvarian cancer (OC) cells typically reprogram their metabolism to promote rapid proliferation. However, the role of long noncoding RNAs (lncRNAs) in the metabolic reprogramming of ovarian cancer, especially in glucose metabolic reprogramming, remains largely unknown. LINC00629 has been reported in our previous study to promote osteosarcoma progression. Upregulated LINC00629 was found to enhance the growth‐suppressive effect of apigenin on oral squamous cell carcinoma. However, the precise function of LINC00629 in ovarian cancer development remains poorly understood. In this study, we found that LINC00629 was significantly downregulated in OC tissues and that low LINC00629 expression was associated with poor survival. Inhibition of LINC00629 was required for increased glycolysis activity and cell proliferation in ovarian cancer. In vivo, overexpression of LINC00629 dramatically inhibited tumor growth and lung metastasis. Mechanistically, LINC00629 interacted with and destabilized c‐Myc, leading to its ubiquitination and proteasome degradation, further resulting in increased expression of downstream glycolysis‐related genes and glucose metabolic reprogramming in OC. Interestingly, HOXB4 bound to the LINC00629 promoter and inhibited its transcription, indicating that LINC00629 is a transcriptional target of HOXB4. Collectively, these findings establish a direct role for LINC00629 in suppressing glucose metabolism, and HOXB4/LINC00629/c‐Myc might serve as a potential biomarker and an effective therapeutic strategy for OC cancer treatment.

RETRACTED: LBX2‐AS1 promotes ovarian cancer progression by facilitating E2F2 gene expression via miR‐455‐5p and miR‐491‐5p sponging

Abstract LBX2‐AS1 is a long non‐coding RNA that facilitates the development of gastrointestinal cancers and lung cancer, but its participation in ovarian cancer development remained uninvestigated. Clinical data retrieved from TCGA ovarian cancer database and the clinography of 60 ovarian cancer patients who received anti‐cancer treatment in our facility were analysed. The overall cell growth, colony formation, migration, invasion, apoptosis and tumour formation on nude mice of ovarian cancer cells were evaluated before and after lentiviral‐based LBX2‐AS1 knockdown. ENCORI platform was used to explore LBX2‐AS1‐interacting microRNAs and target genes of the candidate microRNAs. Luciferase reporter gene assay and RNA pulldown assay were used to verify the putative miRNA‐RNA interactions. Ovarian cancer tissue specimens showed significant higher LBX2‐AS1 expression levels that non‐cancerous counterparts. High expression level of LBX2‐AS1 was significantly associated with reduced overall survival of patients. LBX2‐AS1 knockdown significantly down‐regulated the cell growth, colony formation, migration, invasion and tumour formation capacity of ovarian cancer cells and increased their apoptosis in vitro. LBX2‐AS1 interacts with and thus inhibits the function of miR‐455‐5p and miR‐491‐5p, both of which restrained the expression of E2F2 gene in ovarian cancer cells via mRNA targeting. Transfection of miRNA inhibitors of these two miRNAs or forced expression of E2F2 counteracted the effect of LBX2‐AS1 knockdown on ovarian cancer cells. LBX2‐AS1 was a novel cancer‐promoting lncRNA in ovarian cancer. This lncRNA increased the cell growth, survival, migration, invasion and tumour formation of ovarian cancer cells by inhibiting miR‐455‐5p and miR‐491‐5p, thus liberating the expression of E2F2 cancer‐promoting gene.