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LncRNA H19-Encoded Micropeptide altH19 Promotes DNA Replication and Mitosis in Myeloma Cells by Enhancing the

Yaxin Zhang1,2, Wenjing Li1,2, Xu Cao1,2

  • 1Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.

Cell Proliferation
|June 27, 2025
PubMed

Insights

A novel micropeptide, altH19, derived from H19 long non-coding RNA, drives multiple myeloma progression by promoting cell proliferation and DNA replication. Targeting the altH19-CDK2-RB pathway offers therapeutic potential for this incurable cancer.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Genetics

Background:

  • Micropeptides, translated from alternative open reading frames, are increasingly recognized for their roles in physiological and pathological processes.
  • Multiple myeloma (MM) is a hematological malignancy with limited treatment options due to frequent relapses and poorly understood mechanisms.
  • Understanding novel molecular players in MM pathogenesis is crucial for developing effective therapies.

Purpose of the Study:

  • To investigate the function and molecular mechanism of a novel micropeptide, altH19, in the context of multiple myeloma (MM).
  • To identify potential therapeutic targets within the altH19-mediated signaling pathway in MM.

Main Methods:

  • Identification and characterization of the micropeptide altH19 encoded by the H19 lncRNA.
  • Functional assays including cell proliferation, colony formation, and flow cytometry to assess altH19's impact on myeloma cells.
  • Molecular analyses to elucidate the interaction of altH19 with key cell cycle regulators like CDK2 and RB.
  • In vitro experiments using a CDK2 inhibitor (Seliciclib) to evaluate altH19's effect on drug-suppressed pathways.

Main Results:

  • The micropeptide altH19 is highly expressed in MM patients and significantly promotes myeloma cell proliferation and colony formation.
  • Overexpression of altH19 induces multipolar mitosis by upregulating Aurora B, Centrin 2, and phosphorylated histone H3, enhancing DNA replication.
  • AltH19 directly interacts with phosphorylated CDK2 at threonine 160, enhancing CDK2 and downstream RB phosphorylation.
  • AltH19 can reverse the suppressive effects of the CDK2 inhibitor Seliciclib on CDK2 and RB phosphorylation.

Conclusions:

  • AltH19 is a novel lncRNA-derived micropeptide that plays a pivotal role in promoting multiple myeloma progression.
  • The altH19-CDK2-RB signaling axis is a key mechanism driving myeloma cell proliferation and survival.
  • Targeting the altH19-CDK2-RB axis represents a promising therapeutic strategy for multiple myeloma treatment.
Keywords:
CDK2DNA replicationmicropeptidemitosismultiple myeloma

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