Related Experiment Video

Updated: Jul 14, 2025

Through the Looking Glass: Time-lapse Microscopy and Longitudinal Tracking of Single Cells to Study Anti-cancer Therapeutics
06:00

Through the Looking Glass: Time-lapse Microscopy and Longitudinal Tracking of Single Cells to Study Anti-cancer Therapeutics

Published on: May 14, 2016

11.1K

CADM1 impairs the effect of miR-1246 on promoting cell cycle progression in chemo-resistant leukemia cells

Bei Xie1, Lei Zhao2, Zhewen Zhang3

  • 1Department of Immunology, School of Basic Medical Sciences, Lanzhou University, No. 199 Donggang West Road, Lanzhou, 730000, Gansu, China. xieb@lzu.edu.cn.

BMC Cancer
|October 9, 2023
PubMed

Insights

MicroRNA-1246 (miR-1246) promotes leukemia drug resistance by suppressing CADM1, which regulates cell cycle progression. Inhibiting miR-1246 or restoring CADM1 enhances chemotherapy sensitivity in leukemia.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Genetics

Background:

  • Aberrant cell cycle regulation is critical in leukemia development.
  • MicroRNAs (miRNAs) are implicated in cancer, with dysregulated expression affecting tumorigenesis.
  • Our prior work identified miR-1246 overexpression in chemo-resistant leukemia, linking it to cell cycle and multidrug resistance.

Purpose of the Study:

  • To elucidate the mechanism by which miR-1246 influences chemo-resistance in leukemia.
  • To identify direct targets of miR-1246 involved in leukemia progression.
  • To investigate the therapeutic potential of targeting the miR-1246/CADM1 axis.

Main Methods:

  • Bioinformatics prediction and dual luciferase reporter assays to identify miR-1246 targets.
  • Analysis of CADM1 expression in patient samples and cell lines.
  • Functional assays in K562/ADM and HL-60/RS cells to assess the impact of miR-1246 inhibition and CADM1 interference on drug sensitivity, cell cycle, and apoptosis.
  • Investigation of the role of CDKs/Cyclins complexes in mediating these effects.

Main Results:

  • CADM1 was confirmed as a direct target of miR-1246.
  • CADM1 expression was significantly decreased in relapsed leukemia patients and chemo-resistant cell lines.
  • Inhibition of miR-1246 enhanced Adriamycin sensitivity, induced G0/G1 cell cycle arrest, promoted apoptosis, and restored CADM1 expression.
  • CADM1 interference reversed the enhanced drug sensitivity from miR-1246 inhibition, promoting chemo-resistance via cell cycle regulation.

Conclusions:

  • CADM1 acts as a tumor suppressor by attenuating miR-1246's pro-survival and cell cycle promoting roles in chemo-resistant leukemia.
  • The miR-1246/CADM1 axis, involving CDKs/Cyclins, is a key regulator of multidrug resistance in leukemia.
  • Elevated miR-1246 and reduced CADM1 expression are potential risk factors for leukemia progression and chemo-resistance.
Keywords:
CADM1CDKs/Cyclins axisCell cycleChemo-resistant leukemia cellsmiR-1246

More Related Videos

Studying Cell Cycle-regulated Gene Expression by Two Complementary Cell Synchronization Protocols12:02

Studying Cell Cycle-regulated Gene Expression by Two Complementary Cell Synchronization Protocols

Published on: June 6, 2017

27.4K
Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis11:44

Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis

Published on: March 30, 2019

7.7K

Related Concept Videos

Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
4.8K
M-Cdk Drives Transition Into Mitosis02:15

M-Cdk Drives Transition Into Mitosis

Checkpoints throughout the cell cycle serve as safeguards and gatekeepers, allowing the cell cycle to progress in favorable conditions and slow or halt it in problematic ones. This regulation is known as the cell cycle control system.
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
5.6K
DNA Damage can Stall the Cell Cycle02:37

DNA Damage can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
9.2K
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.6K
Separation of Sister Chromatids02:17

Separation of Sister Chromatids

At the transition from prophase to metaphase, there is a reduction in cohesion along the chromosomal arms, resulting in the resolution of sister chromatids. However, residual cohesin connections remain to hold the sister chromatids together until the transition from metaphase to anaphase. The residual connection prevents any premature separation of sister chromatids, blocking the risks of aneuploidy within the daughter cells.
At the onset of anaphase, separase, a proteolytic enzyme, is...
3.7K
Treatment Resistant Cancers02:56

Treatment Resistant Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
3.3K