Long non-coding RNA HAGLROS regulates the proliferation, migration, and apoptosis of esophageal cancer cells via the HAGLROS-miR-206- NOTCH3 axis

Ling Gai; Yeqing Huang; Lingling Zhao; Feng Li; Zhixiang Zhuang

doi:10.21037/jgo-21-586

Long non-coding RNA HAGLROS regulates the proliferation, migration, and apoptosis of esophageal cancer cells via the HAGLROS-miR-206- NOTCH3 axis

J Gastrointest Oncol. 2021 Oct;12(5):2093-2108. doi: 10.21037/jgo-21-586.

Authors

Ling Gai^#^{1

2}, Yeqing Huang^#², Lingling Zhao³, Feng Li⁴, Zhixiang Zhuang¹

Affiliations

¹ Department of Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, China.
² Department of Chemotherapy, Affiliated Hospital of Nantong University, Nantong, China.
³ Department of Medical Ultrasound, The First People's Hospital of Nantong, Nantong, China.
⁴ Department of Laboratory Medicine, Affiliated Hospital of Nantong University, Nantong, China.

^# Contributed equally.

Abstract

Background: Esophageal cancer (EC) is a common malignant tumor of the digestive tract, the treatment of which involves surgery combined with radiotherapy and chemotherapy, as well as other comprehensive types of treatment. The pathogenesis of EC remains unclear, which hinders the development of clinical therapy and the identification of molecular targets for this disease. Long non-coding RNAs (lncRNAs) have been shown to be associated with the malignant biological behavior of EC, but the specific molecular mechanisms underlying the carcinogenesis of EC are not fully understood.

Methods: Reverse transcription-quantitative PCR (RT-qPCR) was applied to measure the lncRNA HAGLR opposite strand lncRNA (HAGLROS) levels in EC cell lines and tissues. Cell Counting Kit-8 (CCK-8) detection, scratch test, and Transwell assay were performed to determine the proliferation, migration and invasion of EC cell. The interaction between HAGLROS, microRNA (miR)-206, and notch receptor 3 (NOTCH3) was confirmed by RNA immunoprecipitation and dual luciferase reporter gene assays.

Results: HAGLROS is upregulated in esophageal squamous cell carcinoma (ESCC) tissues and predicts poor prognosis. Silent HAGLROS is negatively associated with malignant behavior in EC cells. Low expression of HAGLROS can induce decreased invasive and migratory abilities in EC cells. Downregulated HAGLROS significantly inhibits the proliferation of EC cells and accelerates apoptosis. HAGLROS promotes EC cell tumorigenesis in vivo. HAGLROS participates in the HAGLROS/miR-206/NOTCH3 regulatory axis in EC cells.

Conclusions: HAGLROS may play a role in the progression of EC by modulating the miR-206/NOTCH3 signaling axis, and may be a novel target for the diagnosis and treatment of EC.

Keywords: HAGLR opposite strand lncRNA (HAGLROS); Long non-coding RNA (lncRNA); esophageal carcinoma; microRNA-206 (miR-206); notch receptor 3 (NOTCH3).