LncRNA HOTAIRM1 knockdown inhibits cell glycolysis metabolism and tumor progression by miR-498/ABCE1 axis in non‐small cell lung cancer

Chen, Dongping; Li, Yashan; Wang, Yukang; Xu, Jinlian

doi:10.1007/s13258-021-01052-9

Cited by 13 publications

(12 citation statements)

References 24 publications

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“…Our study was the first to determine that HOTAIRM1 was an upregulated lncRNA in OSCC according to the differential expression analysis, which was subsequently confirmed by its high expression in OSCC cell lines, confirming the relevance between HOTAIRM1 expression and OSCC. However, a review of the literatures relative to HOTAIRM1 showed that HOTAIRM1 was previously explored only in thyroid, ovarian cancer, non-small cell lung cancer, leukemia, and clear cell renal cell carcinoma ( Zhang et al, 2014 ; Chao et al, 2020 ; Hamilton et al, 2020 ; Chen D. et al, 2021 ; Li et al, 2021 ; Liang et al, 2021 ). In leukemia, HOTAIRM1 was considered to be unfavorable and it could activate RHOA/ROCK1 pathway to enhance glucocorticoid resistance by inhibiting ARHGAP18 ( Liang et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Identification and Validation of HOTAIRM1 as a Novel Biomarker for Oral Squamous Cell Carcinoma

Niu

Zhang

et al. 2022

Front. Bioeng. Biotechnol.

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ORAL squamous cell carcinoma (OSCC) is a malignant tumor with the highest incidence among tumors involving the oral cavity maxillofacial region, and is notorious for its high recurrence and metastasis potential. Long non-coding RNAs (lncRNAs), which regulate the genesis and evolution of cancers, are potential prognostic biomarkers. This study identified HOTAIRM1 as a novel significantly upregulated lncRNA in OSCC, which is strongly associated with unfavorable prognosis of OSCC. Systematic bioinformatics analyses demonstrated that HOTAIRM1 was closely related to tumor stage, overall survival, genome instability, the tumor cell stemness, the tumor microenvironment, and immunocyte infiltration. Using biological function prediction methods, including Weighted gene co-expression network analysis (WGCNA), Gene set enrichment analysis (GSEA), and Gene set variation analysis (GSVA), HOTAIRM1 plays a pivotal role in OSCC cell proliferation, and is mainly involved in the regulation of the cell cycle. In vitro, cell loss-functional experiments confirmed that HOTAIRM1 knockdown significantly inhibited the proliferation of OSCC cells, and arrested the cell cycle in G1 phase. At the molecular level, PCNA and CyclinD1 were obviously reduced after HOTAIRM1 knockdown. The expression of p53 and p21 was upregulated while CDK4 and CDK6 expression was decreased by HOTAIRM1 knockdown. In vivo, knocking down HOTAIRM1 significantly inhibited tumor growth, including the tumor size, weight, volume, angiogenesis, and hardness, monitored by ultrasonic imaging and magnetic resonance imaging In summary, our study reports that HOTAIRM1 is closely associated with tumorigenesis of OSCC and promotes cell proliferation by regulating cell cycle. HOTAIRM1 could be a potential prognostic biomarker and a therapeutic target for OSCC.

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Section: Discussionmentioning

confidence: 99%

Identification and Validation of HOTAIRM1 as a Novel Biomarker for Oral Squamous Cell Carcinoma

Niu

Zhang

et al. 2022

Front. Bioeng. Biotechnol.

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“…Recent studies have shown that the function of HOTAIRM1 is different in different types of cancer. In leukemia 38 , glioblastoma 39 , 40 , non-small cell lung cancer 41 , 42 and thyroid cancer 43 , the expression of HOTAIRM1 is upregulated and it functions as an oncogene. However, HOTAIRM1 is downregulated in the hepatocellular carcinoma 40 , colorectal cancer 44 , 45 , ovarian cancer 46 and GC 28 , and is absolutely a suppressor factor.…”

Section: Discussionmentioning

confidence: 99%

The Curcumin Analog Da0324 Inhibits the Proliferation of Gastric Cancer Cells via HOTAIRM1/miR-29b-1-5p/PHLPP1 Axis

Chen

et al. 2022

J. Cancer

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Background: Our previous study has shown that Da0324, a curcumin analog, exhibited significantly improved stability and antitumor activity. However, the molecular mechanisms of action of Da0324 remain poorly understood. Long non-coding RNA (lncRNA) has been shown to play a key role in tumor progression. Here, we aim to investigate the molecular mechanisms underlying the anti-cancer activity of Da0324 by regulating the lncRNA HOTAIRM1. Methods: Gastric cancer cell lines were treated with Da0324 and/or transfected with lentiviral vector expressing HOTAIRM1 shRNA, and/or miR-29b-1-5p mimics and/or small interference RNA (siRNA) against PHLPP1, or HOTAIRM1 siRNA or lentiviral vector expressing HOTAIRM1, as needed. The expression of HOTAIRM1, miR-29b-1-5p and PHLPP1 in GC cells was determined by Real-Time PCR. Cell growth was examined by CCK-8 assay and colony formation assay in vitro . The targeted relationship between HOTAIRM1 and miR-29b-1-5p was verified by luciferase reporter gene assay. PHLPP1 protein expression was examined by Western blotting. Results: Da0324 increased the expression of HOTAIRM1 in GC cells. HOTAIRM1 expression was significantly down-regulated in GC tissues, and the low expression of HOTAIRM1 was associated with the shorter survival rate of GC patients based on the TCGA database. Knockdown of HOTAIRM1 promoted GC cell proliferation whereas overexpression of HOTAIRM1 inhibited GC cell proliferation as demonstrated by CCK-8 and colony formation assays. Moreover, knockdown of HOTAIRM1 reversed the Da0324-mediated growth inhibition of GC cells. Furthermore, HOTAIRM1 acted as a sponge for miR-29b-1-5p and PHLPP1 is regulated by the HOTAIRM1/miR-29b-1-5p axis in GC cells. Overexpression of miR-29b-1-5p or knockdown of PHLPP1 reversed the ability of Da0324 to inhibit the growth of GC cells. Conclusions: Our data suggest that Da0324 exerts antitumor activity by regulating HOTAIRM1/miR-29b-1-5p/PHLPP1 axis in GC cells, and provide new insights into the anti-cancer mechanism of Da0324.

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“…HOTAIRM1 (HOXA transcript antisense RNA myeloid-specific 1), a lncRNA which has been found to be abnormally expressed in various tumors in recent years and dramatically overexpressed in NSCLC tissues, was found to facilitate glycolysis and tumor progression in NSCLC via miR-498 sequestering and ATP binding cassette subfamily E member 1 (ABCE1) enhancement [ 37 , 78 ].…”

Section: Glucose Metabolismmentioning

confidence: 99%

“…Using LC tissues, 15 lncRNAs and 17 circRNAs have been shown to be potentially diagnostic biomarkers. The lncRNAs include DUXAP8, IGFBP4-1, BCYRN1, CRYBG3, LINC00243, AC020978, LINC01123, HOXA11-AS, ABHD11-AS1, AL355338, HOTAIRM1, CTD-2245E15.3, CCAT1, MINCR, and PVT1-5 [ 22 , 23 , 25 , 26 , 28 , 31 , 33 – 37 , 49 – 51 , 53 ]. The circRNAs comprise circMYLK, circMAGI3, circAGFG1, circSLC25A16, circ-MEMO1, circDCUN1D4, circ-ERBB2, circTADA2A, circ-PGC, circPUM1, circ_0000517, circ-PITX1, circ_0006677, circNFIX, circ-ENO1, circ-LDLRAD3, and circ_0003028 [ 20 , 24 , 29 , 30 , 32 , 39 – 48 , 52 , 55 ].…”

Section: Current Evidence On the Potential Clinical Utility Of Lncrna...mentioning

confidence: 99%

Long Noncoding RNAs and Circular RNAs in the Metabolic Reprogramming of Lung Cancer: Functions, Mechanisms, and Clinical Potential

Zhou

Zhan

Jiang

et al. 2022

Oxidative Medicine and Cellular Longevity

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As key regulators of gene function, long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) are generally accepted to be involved in lung cancer pathogenesis and progression. Recent research has clarified the phenomenon of metabolic reprogramming in lung cancer because of its significant role in tumor proliferation, migration, invasion, metastasis, and other malignant biological behaviors. Emerging evidence has also shown a relationship between the aberrant expression of lncRNAs and circRNAs and metabolic reprogramming in lung cancer tumorigenesis. This review provides insight regarding the roles of different lncRNAs and circRNAs in lung cancer metabolic reprogramming, by how they target transporter proteins and key enzymes in glucose, lipid, and glutamine metabolic signaling pathways. The clinical potential of lncRNAs and circRNAs as early diagnostic biomarkers and components of therapeutic strategies in lung cancer is further discussed, including current challenges in their utilization from the bench to the bedside and how to adopt a proper delivery system for their therapeutic use.

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LncRNA HOTAIRM1 knockdown inhibits cell glycolysis metabolism and tumor progression by miR-498/ABCE1 axis in non‐small cell lung cancer

Cited by 13 publications

References 24 publications

Identification and Validation of HOTAIRM1 as a Novel Biomarker for Oral Squamous Cell Carcinoma

Identification and Validation of HOTAIRM1 as a Novel Biomarker for Oral Squamous Cell Carcinoma

The Curcumin Analog Da0324 Inhibits the Proliferation of Gastric Cancer Cells via HOTAIRM1/miR-29b-1-5p/PHLPP1 Axis

Long Noncoding RNAs and Circular RNAs in the Metabolic Reprogramming of Lung Cancer: Functions, Mechanisms, and Clinical Potential

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