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Long Non-Coding RNA HAND2 Antisense RNA 1 Inhibits Colorectal Cancer Development by Sponging microRNA-3118/Leptin

Cen Yi1, Chunxiang Zhao2, Cong Peng3

  • 1Department of Clinical Laboratory, Wuhan No.1 Hospital, Wuhan, Hubei, China.

Annals of Clinical and Laboratory Science
|March 8, 2023
PubMed
Abstract

Insights

Long non-coding RNA HAND2-AS1 inhibits colorectal cancer (CRC) progression by targeting the miR-3118-LEPR pathway. Upregulating HAND2-AS1 suppresses tumor growth, migration, and promotes apoptosis in CRC.

Area of Science:

  • Molecular Biology
  • Oncology
  • Genetics

Background:

  • Colorectal cancer (CRC) remains a significant health concern with complex molecular underpinnings.
  • Long non-coding RNAs (lncRNAs) are increasingly recognized for their roles in cancer development and progression.
  • Understanding the specific functions of lncRNAs like HAND2-AS1 is crucial for developing novel therapeutic strategies.

Purpose of the Study:

  • To investigate the functional role of long non-coding RNA HAND2 antisense RNA 1 (HAND2-AS1) in colorectal cancer (CRC).
  • To elucidate the molecular mechanism by which HAND2-AS1 influences CRC progression.
  • To explore the potential of HAND2-AS1 as a therapeutic target for CRC.

Main Methods:

  • Quantitative analysis of HAND2-AS1, microRNA (miR)-3118, and leptin receptor (LEPR) expression using RT-qPCR and Western blot.
  • Assessment of molecular interactions using RNA-binding protein immunoprecipitation (RIP) and luciferase reporter assays.
  • In vitro functional assays (proliferation, migration, apoptosis) in CRC cell lines and in vivo studies using a CRC xenograft mouse model.

Main Results:

  • HAND2-AS1 expression was found to be downregulated in CRC cell lines and tumor tissues.
  • Overexpression of HAND2-AS1 inhibited CRC cell proliferation and migration, induced apoptosis, and suppressed tumor growth in vivo.
  • HAND2-AS1 acts as a molecular sponge for miR-3118, which is upregulated in CRC and promotes proliferation while inhibiting apoptosis.
  • miR-3118 targets LEPR, a gene downregulated in CRC, and its effects are counteracted by LEPR overexpression.

Conclusions:

  • HAND2-AS1 exerts an inhibitory effect on colorectal cancer progression.
  • The mechanism involves the HAND2-AS1/miR-3118/LEPR axis, where HAND2-AS1 sponges miR-3118, thereby modulating LEPR expression.
  • These findings suggest HAND2-AS1 as a potential therapeutic target for colorectal cancer treatment.
Keywords:
Colorectal cancerLEPRlncRNA HAND2-AS1miR-3118

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