LncRNA KCNQ1OT1 sponges miR-34c-5p to promote osteosarcoma growth via ALDOA enhanced aerobic glycolysis

Abstract

Metabolic switch from oxidative phosphorylation to aerobic glycolysis, which is also called the Warburg effect, is a hallmark of osteosarcoma (OS) and leads to the enhancement of cell chemoresistance, growth, metastasis, and invasion. Emerging evidence indicates that long non-coding RNA (lncRNA) plays a crucial role in the Warburg effect of cancer cells. Here, we report that lncRNA KCNQ1OT1 was upregulated in OS. Meanwhile, functional experiments demonstrated that the KCNQ1OT1 facilitated proliferation and suppressed apoptosis of OS cells. In addition, KCNQ1OT1 contributed to the Warburg effect by stimulating aldolase A (ALDOA) expression. Furthermore, using bioinformatics analysis, luciferase reporter, RNA immunoprecipitation, and RNA pull-down assay, we identified that KCNQ1OT1 functions as a competing endogenous RNA (ceRNA) by sponging miR-34c-5p, which inhibited ALDOA expression by directly targeting its 3ʹUTR. Taken together, these data identified a key role of KCNQ1OT1 in glucose metabolism reprogramming of OS. Targeting the KCNQ1OT1/miR-34c-5p/ALDOA axis may be a potential therapeutic target in OS treatment.

KCNQ1OT1 lncRNA affects the proliferation, apoptosis, and chemoresistance of small cell lung cancer cells via the JAK2/ STAT3 axis

“…Similarly, we found that KCNQ1OT1 promoted the proliferation, cloning, migration, and invasion of cancer cells. In addition, the knockdown of KCNQ1OT1 has been reported to significantly induce the apoptosis of osteosarcoma cells (28) and nonsmall cell lung cancer cells (20), while the silencing of KCNQ1OT1 was shown to impede methotrexate-resistant colorectal cancer cell tumor growth in nude mice (22). In vivo, we discovered that the downregulation of KCNQ1OT1 repressed the volume growth and reduced the weight of the tumors, indicating that KCNQ1OT1 may acts as a carcinogenic and chemo-resistant biomarker for SCLC.…”

Aldolase A Enhances Intrahepatic Cholangiocarcinoma Proliferation and Invasion through Promoting Glycolysis

“…ALDOA is a ubiquitous glycolytic enzyme that drives the glycolytic metabolism pathway in mammalian cells and is mainly expressed in adult muscle tissue. Overexpression of ALDOA has been observed in a variety of cancers including renal clear cell carcinoma [37], lung squamous cell carcinoma [38], colorectal cancer [39], osteosarcoma [40], and oral squamous cells [41], suggesting that glycolysis is enhanced in these cancer cells. However, the current expression of ALDOA in ICC is still unclear, and its regulatory mechanisms involved in tumor progression have yet to be studied.…”

“…Until 2019, Qin et al found that Itaconate can inhibit ALDOA's enzymatic activity by modifying Cys73 and Cys339 of ALDOA without changing its protein expression level [12]. As an important metabolic enzyme in the glycolytic pathway, ALDOA has been shown to be involved in the regulation of the progression of a variety of tumors [37][38][39][40][41]. Our study also confirmed that the high expression of ALDOA promoted the progress of ICC, and Itaconate can directly inhibit the glycolysis level of ICC tumor cells and thus affect tumor progression.…”

LINC01816 promotes the migration, invasion and epithelial‑mesenchymal transition of thyroid carcinoma cells by sponging miR‑34c‑5p and regulating CRABP2 expression levels

“…Previous evidence suggested that miR-34c-5p expression was closely associated with a poor prognosis and unfavorable clinicopathological parameters (20,21). Shen et al indicated that the lncRNA KCNQ1 opposite strand/antisense transcript 1 sponged miR-34c-5p to promote osteosarcoma growth via aldolase, fructose-bisphosphate A-enhanced aerobic glycolysis (22). Numerous other studies have revealed that miR-34c-5p was closely related to the development of numerous types of human malignant cancer (23)(24)(25).…”