Long non‑coding RNA HOTAIR promotes cancer cell energy metabolism in pancreatic adenocarcinoma by upregulating hexokinase‑2

Abstract

Hox transcript antisense RNA (HOTAIR) is a long non-coding RNA (lncRNA) that serves a key role in the pathogenesis of various types of cancer, including pancreatic adenocarcinoma. However, the diagnostic and prognostic values of HOTAIR in pancreatic adenocarcinoma, as well as its involvement in cancer cell energy metabolism, remain unclear. In the present study, tumor tissues and adjacent healthy tissues were collected from patients with pancreatic adenocarcinoma, and blood samples were collected from patients and healthy controls. Expression levels of HOTAIR and hexokinase-2 (HK2) were detected by reverse transcription-quantitative polymerase chain reaction. All patients were followed up for 5 years, and the diagnostic and prognostic values of serum HOTAIR levels were investigated by receiver operating characteristic curve and survival analyses, respectively. Pancreatic adenocarcinoma cell lines overexpressing HOTAIR and HK2 were established, and the effects on cell proliferation, lactate production, glucose uptake and ATP production were detected by Cell Counting Kit-8, lactate, glucose uptake and ATP assays, respectively. The protein expression was detected by western blot analysis. The results revealed that HOTAIR and HK2 expression levels were increased in tumor tissues compared with adjacent healthy tissues. The serum levels of HOTAIR and HK2 were higher in patients with pancreatic cancer compared with healthy controls. The serum levels of these two factors may be used to accurately predict pancreatic adenocarcinoma and its prognosis. HOTAIR and HK2 overexpression led to the promotion of tumor cell proliferation. HOTAIR overexpression increased lactate production, glucose uptake and ATP production. Furthermore, it promoted HK2 expression, however HK2 overexpression displayed no significant effects on HOTAIR expression levels. Therefore, it was concluded that the lncRNA HOTAIR may promote cancer cell energy metabolism in pancreatic adenocarcinoma by upregulating HK2.

Regulatory Role of Hexokinase 2 in Modulating Head and Neck Tumorigenesis

“…Interestingly, mitochondrial TIGAR-HK2 complex upregulated HK2 and hypoxia-inducible factor 1 activity limiting reactive oxygen species production and protecting from tumor cell death under hypoxic condition implying that p53 could be an essential key regulator for HK2-mediated oncogenesis (26,30,48). In addition to signaling factors, HK2 regulated by epigenetic mediators including microRNAs (32,(52)(53)(54)(55), long non-coding RNAs (56)(57)(58), and histone/DNA methylation (59) are also important to modulate HK2-mediated tumorigenicity. Taken together, HK2 seems to be a master promoting factor in controlling carcinogenesis in different cancers; to date, however, the role of HK2 in controlling head and neck squamous cell carcinoma (HNSCC) development was rarely focused.…”

<p>lncRNA TM4SF1-AS1 Activates the PI3K/AKT Signaling Pathway and Promotes the Migration and Invasion of Lung Cancer Cells</p>

“…But recently, IncRNAs have been proved to be important regulators participating in the development of diseases, in particular cancer. 8,9 These lncRNAs could regulate the biological behaviors of tumor cells in terms of genomic stability, 10,11 transcription, 12,13 metabolism 14 and so on. Nevertheless, studies of lncRNAs in cancer are still at an early stage and need to be examined in more detail.…”

<p>LncRNA RP11-422N16.3 Inhibits Cell Proliferation and EMT, and Induces Apoptosis in Hepatocellular Carcinoma Cells by Sponging miR-23b-3p</p>

“…30,31 Common features of tumor metabolism include changes in glucose aerobic glycolysis, glutamine metabolism, tricarboxylic acid cycle, and anabolism, these characteristics may become a new development direction for the treatment of cancer, thereby avoiding and overcoming the genetic heterogeneity of tumors, and revealing the significance of research on the metabolism of substances in tumor cells. 32,33 Therefore, we previously performed a coexpression analysis of RP11-422N16.3 and a metabolic enzyme-related gene, and found that dimethylglycine dehydrogenase (DMGDH) was significantly positively correlated with RP11-422N16.3 expression, and low expression of DMGDH was a significant adverse factor in the prognosis of liver cancer patients. DMGDH has two splicing isoforms.…”