Long non‑coding RNA urothelial cancer associated�1 regulates radioresistance via the hexokinase�2/glycolytic pathway in cervical cancer

Фан, Ли; Huang, Chunxian; Li, Jing; Gao, Tian; Lin, Zhongqiu; Yao, Tingting

doi:10.3892/ijmm.2018.3778

Cited by 50 publications

(50 citation statements)

References 31 publications

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“…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.…”

Section: Introductionmentioning

confidence: 99%

Regulatory Role of Hexokinase 2 in Modulating Head and Neck Tumorigenesis

Huang²,

Hsieh³

et al. 2020

Front. Oncol.

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To support great demand of cell growth, cancer cells preferentially obtain energy and biomacromolecules by glycolysis over mitochondrial oxidative phosphorylation (OxPhos). Among all glycolytic enzymes, hexokinase (HK), a rate-limiting enzyme at the first step of glycolysis to catalyze cellular glucose into glucose-6-phosphate, is herein emphasized. Four HK isoforms, HK1-HK4, were discovered in nature. It was shown that HK2 expression is enriched in many tumor cells and correlated with poorer survival rates in most neoplastic cells. HK2-mediated regulations for cell malignancy and mechanistic cues in regulating head and neck tumorigenesis, however, are not fully elucidated. Cellular malignancy index, such as cell growth, cellular motility, and treatment sensitivity, and molecular alterations were determined in HK2-deficient head and neck squamous cell carcinoma (HNSCC) cells. By using various cancer databases, HK2, but not HK1, positively correlates with HNSCC progression in a stage-dependent manner. A high HK2 expression was detected in head and neck cancerous tissues compared with their normal counterparts, both in mouse and human subjects. Loss of HK2 in HNSCC cells resulted in reduced cell (in vitro) and tumor (in vivo) growth, as well as decreased epithelial-mesenchymal transition-mediated cell movement; in contrast, HK2-deficient HNSCC cells exhibited greater sensitivity to chemotherapeutic drugs cisplatin and 5-fluorouracil but are more resistant to photodynamic therapy, indicating that HK2 expression could selectively define treatment sensitivity in HNSCC cells. At the molecular level, it was found that HK2 alteration drove metabolic reprogramming toward OxPhos and modulated oncogenic Akt and mutant TP53-mediated signals in HNSCC cells. In summary, the present study showed that HK2 suppression could lessen HNSCC oncogenicity and modulate therapeutic sensitivity, thereby being an ideal therapeutic target for HNSCCs.

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Section: Introductionmentioning

confidence: 99%

Regulatory Role of Hexokinase 2 in Modulating Head and Neck Tumorigenesis

Huang²,

Hsieh³

et al. 2020

Front. Oncol.

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“…1 shows four lncRNAs related to glycolysis: (1) lncRNA Ftx promotes the expression of peroxisome proliferator-activated receptor γ (PPARγ), and PPARγ upregulates the expression of enzymes in carbohydrate metabolism, which ultimately enhances aerobic glycolysis in HCC. In addition, the alterations in lactate production, glucose uptake and the enzyme expression induced by Ftx can be counteracted by downregulating the expression of PPARγ [28]; (2) lncRNA UCA1 promotes glycolysis by upregulating hexokinase 2 (HK2) in cervical cancer [29]; (3) lncRNA-p23154 suppresses the expression of miR-378a-3p, and miR-378a-3p can promote Glut1-mediated glycolysis in oral squamous cell cancer by binding and inhibiting Glut1 [30]; and (4) lncRNA CRYBG3 increases the expression of lactate dehydrogenase A (LDHA), and LDHA promotes glycolysis in lung cancer. Furthermore, glycolysis can enhance cell proliferation [31].…”

Section: Promoting Glycometabolismmentioning

confidence: 99%

Recent Progress in Characterizing Long Noncoding RNAs in Cancer Drug Resistance

Zhao¹,

Shan²,

He³

et al. 2019

J. Cancer

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Drug resistance is an important cause of failure in cancer chemotherapies. A large number of long noncoding RNAs (lncRNAs) have been found to be related to drug resistance in cancers. Therefore, lncRNAs provide potential targets for cancer therapies. The lncRNAs involved in cancer drug resistance are attracting interest from an increasing number of researchers. This review summarizes the latest research on the mechanisms and functions of lncRNAs in cancer drug resistance and envisages their future developments and therapeutic applications. This research suggests that lncRNAs regulate drug resistance through multiple mechanisms. LncRNAs do not affect drug resistance directly; usually, they do so by regulating the expression of some intermediate regulatory factors. In addition, lncRNAs exhibit a diversity of functions in cancer drug resistance. The overexpression of most lncRNAs promotes drug resistance, while a few lncRNAs have inhibitory effects.

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“…Long non-coding RNAs (lncRNAs) are a family of non-coding RNAs (ncRNAs) that have less than 200 bases in length and possess limited ability for protein-coding (11)(12)(13)(14). Numerous studies have confirmed that dysregulation of lncRNA expression is associated with the development of a number of tumors (15)(16)(17). It is well established that lncRNAs play important roles in the regulation of a battery of cellular and biological processes, including development, differentiation, de-differentiation, proliferation, autophagy and apoptosis (18).…”

Section: Introductionmentioning

confidence: 99%

lncRNA CASC2/miR‑18a‑5p axis regulates the malignant potential of nasopharyngeal carcinoma by targeting RBBP8

et al. 2018

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Nasopharyngeal carcinoma (NPC) is a prevalent head and neck tumor which has a high mortality rate in Southeast Asia, especially in Southern China. Cancer susceptibility candidate 2 (CASC2) is a newly identified long non-coding RNA (lncRNA) that has been found to play a suppressive role in several types of tumors. However, the expression and functional role of CASC2 in NPC are still unclear. In the present study, using NPC tissues, cells and transplanted mice, we investigated the mechanism of CASC2-mediated regulation of NPC. We showed that the CASC2 level is reduced in NPC tissues and cells. CASC2 downregulation promoted proliferation and inhibited apoptotic cell death in NPC cells. In contrast, CASC2 upregulation inhibited proliferation and increased apoptosis. There were putative binding sites of microRNA (miR)-18a-5p in the promoter of CASC2. The level of miR-18a-5p was upregulated in NPC tissues and cells. We further confirmed that CASC2 could directly bind with miR-18a-5p and inhibit miR-18a-5p expression, using reporter gene and RNA immunoprecipitation assays. miR-18a-5p suppressed CASC2 upregulation-mediated decrease in proliferation and increase in apoptotic cell death. Bioinformatics predicted the putative binding site of miR-18a-5p in the 3' untranslated region of C-terminal binding protein interacting protein (CtIP)/RBBP8. It was further confirmed that miR-18a-5p could directly bind with RBBP8 and inhibit RBBP8 expression. Downregulation of RBBP8 inhibited the anti-miR-18a-5p-mediated increase in apoptosis and decrease in proliferation. Downregulation of CASC2 increased tumor growth, increased the level of miR-18a-5p and decreased RBBP8 expression in vivo. In summary, CASC2 regulates NPC malignancy through modulation of RBBP8 via sponging miR-18a-5p. Our findings highlight the CASC2/miR-18a-5p/RBBP8 axis in NPC pathogenesis and provide new biomarkers and potential targets for the therapy of NPC. lncRNA CASC2/miR-18a-5p axis regulates the malignant potential of nasopharyngeal carcinoma by targeting RBBP8

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Long non‑coding RNA urothelial cancer associated�1 regulates radioresistance via the hexokinase�2/glycolytic pathway in cervical cancer

Cited by 50 publications

References 31 publications

Regulatory Role of Hexokinase 2 in Modulating Head and Neck Tumorigenesis

Regulatory Role of Hexokinase 2 in Modulating Head and Neck Tumorigenesis

Recent Progress in Characterizing Long Noncoding RNAs in Cancer Drug Resistance

lncRNA CASC2/miR‑18a‑5p axis regulates the malignant potential of nasopharyngeal carcinoma by targeting RBBP8

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