Related Experiment Video

Updated: Jun 18, 2026

Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
11:44

Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis

Published on: March 30, 2019

MicroRNA-34a is an important component of PRIMA-1-induced apoptotic network in human lung cancer cells

Wenrui Duan1, Li Gao, Xin Wu

  • 1The Ohio State University College of Medicine and Public Health, Columbus, OH, USA. wenrui.duan@osumc.edu

International Journal of Cancer
|November 19, 2009
PubMed

Insights

The small molecule PRIMA-1 induces apoptosis in lung cancer cells with mutant p53 by activating microRNA-34a. This finding offers a new therapeutic strategy for lung cancer by restoring tumor suppressor function.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Pharmacology

Background:

  • Over 50% of lung cancers harbor p53 mutations, making p53 restoration a key therapeutic target.
  • The small molecule PRIMA-1 can restore p53 tumor suppressor function and induce apoptosis in cancer cells.
  • The precise mechanism of PRIMA-1-induced apoptosis is not fully understood.

Purpose of the Study:

  • To investigate the mechanism of apoptosis induced by PRIMA-1 in human lung cancer cell lines.
  • To determine the role of p53 status in PRIMA-1's apoptotic effects.
  • To elucidate the involvement of microRNA-34a in PRIMA-1-mediated apoptosis.

Main Methods:

  • Utilized Western immunoblot analysis, TaqMan microRNA real-time PCR, cell viability assays, and flow cytometry.
  • Tested PRIMA-1 effects on lung cancer cell lines with mutant, wild-type, and null p53.
  • Performed microRNA-34a knockdown experiments to assess its role in apoptosis.

Main Results:

  • PRIMA-1 induced significant apoptosis in lung cancer cells with mutant p53 (H211, H1155) but showed less toxicity in wild-type (A549) or null (H1299) p53 cells.
  • Western blot analysis confirmed PARP cleavage and p53 phosphorylation in PRIMA-1-treated mutant p53 cells.
  • PRIMA-1 treatment upregulated microRNA-34a expression, and its knockdown reduced PRIMA-1-induced apoptosis.

Conclusions:

  • MicroRNA-34a is a crucial component of the apoptotic pathway activated by PRIMA-1 in lung cancer cells with mutant p53.
  • PRIMA-1's efficacy is linked to the presence of mutant p53, suggesting a targeted therapeutic approach.
  • These findings highlight microRNA-34a as a potential mediator in PRIMA-1's anti-cancer activity.

More Related Videos

A Reporter Assay to Analyze Intronic microRNA Maturation in Mammalian Cells06:48

A Reporter Assay to Analyze Intronic microRNA Maturation in Mammalian Cells

Published on: June 16, 2022

An In Vitro Protocol for Evaluating MicroRNA Levels, Functions, and Associated Target Genes in Tumor Cells09:45

An In Vitro Protocol for Evaluating MicroRNA Levels, Functions, and Associated Target Genes in Tumor Cells

Published on: May 21, 2019

Related Concept Videos

MicroRNAs01:22

MicroRNAs

MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...
MicroRNAs01:22

MicroRNAs

MicroRNA (miRNA) are short, regulatory RNA transcribed from introns—non-coding regions of a gene—or intergenic regions—stretches of DNA present between genes. Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA ends...
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
piRNA - Piwi-interacting RNAs02:57

piRNA - Piwi-interacting RNAs

PIWI-interacting RNAs, or piRNAs, are the most abundant short non-coding RNAs. More than 20,000 genes have been found in humans that code for piRNAs while only 2000 genes have been found for miRNAs. piRNAs can act at the transcriptional and post-transcriptional levels and have a vital role in silencing transposable elements present in germ cells. They are also involved in epigenetic silencing and activation. Previously, they were thought to function only in germ cells but new evidence suggests...
Experimental RNAi02:15

Experimental RNAi

RNA interference (RNAi) is a cellular mechanism that inhibits gene expression by suppressing its transcription or activating the RNA degradation process. The mechanism was discovered by Andrew Fire and Craig Mello in 1998 in plants. Today, it is observed in almost all eukaryotes, including protozoa, flies, nematodes, insects, parasites, and mammals. This precise cellular mechanism of gene silencing has been developed into a technique that provides an efficient way to identify and determine the...
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 daughter...