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

Abstract

Background

Non-small cell lung cancer (NSCLC) is a major contributor of cancer-related mortality. Long non-coding RNAs (lncRNAs) are indicated to participate in the pathogenesis of NSCLC.

Objective

In this research, the effects of lncRNA HOXA transcript antisense RNA, myeloid-specific 1 (HOTAIRM1) on NSCLC progression and underlying mechanism were revealed.

Methods

The expression levels of HOTAIRM1 and microRNA-498 (miR-498) were detected by quantitative real time polymerase chain reaction (qRT-PCR) in NSCLC tissues, cells or exosomes. The protein expression of CD63, CD81, hexokinase 2 (HK2) and ATP binding cassette subfamily E member 1 (ABCE1) was determined by western blot. Cell viability, apoptosis, migration and invasion were investigated by cell counting kit-8 (CCK-8), flow cytometry, transwell migration and invasion assays, respectively. Cell glycolysis metabolism was revealed by glucose uptake and lactate production assays and western blot analysis. The binding relationship between miR-498 and HOTAIRM1 or ABCE1 was predicted by DIANA-LncBase v2 and starBase online database, and identified by dual-luciferase reporter assay. The effects of HOTAIRM1 on NSCLC growth in vivo were revealed by in vivo tumor formation assay.

Results

HOTAIRM1 expression was dramatically upregulated, whereas miR-498 expression was significantly downregulated in NSCLC tissues cells or exosomes as compared to control groups. Mechanistically, HOTAIRM1 knockdown repressed cell viability, migration, invasion and glycolysis metabolism, whereas induced cell apoptosis in NSCLC; however, miR-498 inhibitor hindered these effects. Functionally, HOTAIRM1 functioned as a sponge of miR-498 and miR-498 targeted ABCE1. In addition, HOTAIRM1 silencing inhibited NSCLC growth in vivo by downregulating ABCE1 and upregulating miR-498 expression.

Conclusions

HOTAIRM1 knockdown repressed cell glycolysis metabolism and tumor development by reducing ABCE1 expression through sponging miR-498 in NSCLC, which provided a theoretical basis for further studying NSCLC progression.

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Abbreviations

NSCLC:

Non-small cell lung cancer

lncRNAs:

Long non-coding RNAs

HOTAIRM1:

lncRNA HOXA transcript antisense RNA, myeloid-specific 1

ABCE1:

ATP binding cassette subfamily E member 1

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Correspondence to Jinlian Xu.

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Dongping Chen, Yashan Li, Yukang Wang and Jinlian Xu The authors declare that they have no financial conflicts of interest.

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This study had been approved by the The First People’s Hospital of Jingmen. Informed consent was obtained from all individual participants included in the study.

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Chen, D., Li, Y., Wang, Y. et al. LncRNA HOTAIRM1 knockdown inhibits cell glycolysis metabolism and tumor progression by miR-498/ABCE1 axis in non‐small cell lung cancer. Genes Genom 43, 183–194 (2021). https://doi.org/10.1007/s13258-021-01052-9

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Keywords

  • lncRNAs
  • HOTAIRM1
  • miR-498
  • ABCE1
  • NSCLC