miR-634 Activates the Mitochondrial Apoptosis Pathway and Enhances Chemotherapy-Induced Cytotoxicity

Naoto Fujiwara1, Jun Inoue2, Tatsuyuki Kawano3

  • 1Department of Molecular Cytogenetics, Medical Research Institute and Graduate School of Medical and Dental Science, Tokyo Medical and Dental University, Tokyo, Japan. Department of Esophageal and General Surgery, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan.

Cancer Research
|July 29, 2015
PubMed

Insights

MicroRNAs (miRNAs) like miR-634 can target multiple cancer-causing genes. Overexpressing miR-634 may overcome chemotherapy resistance by activating cell death pathways in cancer cells.

Area of Science:

  • Molecular Biology
  • Oncology
  • Biochemistry

Background:

  • Chemotherapy resistance in cancer is a major clinical challenge.
  • Tumor-suppressing microRNAs (miRNAs) offer potential therapeutic strategies.
  • Cytoprotective mechanisms in resistant cancer cells warrant investigation.

Purpose of the Study:

  • To investigate the role of miR-634 in cancer therapy.
  • To determine if miR-634 can overcome chemotherapy resistance.
  • To elucidate the molecular mechanisms by which miR-634 affects cancer cells.

Main Methods:

  • Overexpression of miR-634 in cancer cells.
  • Analysis of the mitochondrial apoptotic pathway.
  • Targeting genes involved in homeostasis, anti-apoptosis, antioxidant ability, and autophagy.
  • Assessment of chemotherapy-induced cytotoxicity in esophageal squamous cell carcinoma models.

Main Results:

  • Overexpression of miR-634 activates the mitochondrial apoptotic pathway.
  • miR-634 concurrently targets genes regulating mitochondrial homeostasis, anti-apoptosis, antioxidant capacity, and autophagy.
  • Enforced miR-634 expression enhances chemotherapy-induced cytotoxicity in esophageal cancer models.

Conclusions:

  • miR-634 acts as a tumor suppressor by inducing apoptosis.
  • Reversing miR-634-mediated cytoprotective processes can enhance cancer therapy.
  • Targeting miR-634 presents a potential strategy to combat chemotherapy resistance.

Related Concept Videos

Chemotherapy-Induced Nausea and Vomiting: Cannabinoids01:21

Chemotherapy-Induced Nausea and Vomiting: Cannabinoids

Tetrahydrocannabinol (THC) is a phytocannabinoid that primarily interacts with the CB1 receptor, a type of G protein-coupled receptor (GPCR) predominantly in and around the chemoreceptor trigger zone (CTZ) and emetic center. THC also blocks the serotonin receptor activity in the dorsal vagal complex (DVC) by inhibiting serotonin release. THC exerts its anti-emetic effects through these interactions, which are beneficial for patients undergoing chemotherapy.
Two synthetic agonists of THC,...
721
Chemotherapy-Induced Nausea and Vomiting: Dopamine Receptor Antagonists01:29

Chemotherapy-Induced Nausea and Vomiting: Dopamine Receptor Antagonists

Dopamine receptor antagonists, also known as antipsychotic agents, are critical in managing chemotherapy-induced vomiting. These antiemetic agents block dopamine receptors in the chemoreceptor trigger zone (CTZ), inhibiting signal transmission to the vomiting center. Antipsychotic agents encompass phenothiazines (PTZ), butyrophenones, benzamides, and thienobenzodiazepines (Zyprexa), which are utilized for their antiemetic and sedative properties.
Phenothiazines, such as prochlorperazine...
839
Apoptosis01:30

Apoptosis

Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size...
14.3K
Chemotherapy-Induced Nausea and Vomiting: 5-HT3 Receptor Antagonists01:27

Chemotherapy-Induced Nausea and Vomiting: 5-HT3 Receptor Antagonists

5-HT3 receptor antagonists, such as dolasetron, granisetron (Kytril), ondansetron (Zofran), and palonosetron (Axoli), are crucial in managing chemotherapy-induced nausea and vomiting (CINV) and postoperative nausea. These drugs selectively block 5-HT3 receptors in the visceral vagal and spinal afferent nerves, chemoreceptor trigger zone, and the vomiting center. They have a rapid onset of action and can be given as a single dose before chemotherapy. Ondansetron and granisetron, in particular,...
630
Chemotherapy-Induced Nausea and Vomiting: Neurokinin-1 Receptor Antagonists01:28

Chemotherapy-Induced Nausea and Vomiting: Neurokinin-1 Receptor Antagonists

Neurokinin 1 (NK1) receptors are distributed across the GI tract, vagal afferents, and key CNS regions including the central vomiting center and chemoreceptor trigger zone (CTZ) Chemotherapy agents stimulate enterochromaffin cells in the gastrointestinal (GI) tract to release large amounts of substance P (SP). SP is a neuropeptide released by specific sensory nerves in response to many different stressors, including those in the GI mucosa affected by chemotherapy.  SP binds and activates...
611
Animal Mitochondrial Genetics02:59

Animal Mitochondrial Genetics

Among all the organelles in an animal cell, only mitochondria have their own independent genomes. Animal mitochondrial DNA is a double-stranded, closed-circular molecule with around 20,000 base pairs. Mitochondrial DNA is unique in that one of its two strands, the heavy, or H, -strand is guanine rich, whereas the complementary strand is cytosine rich and called the light, or L, -strand. Compared to nuclear DNA, mitochondrial DNA has a very low percentage of non-coding regions and is marked by...
9.0K