miR-138-5p targets MCU to inhibit mitochondrial biogenesis and colorectal cancer growth

Jianjun Zhu1, Chunle Zhang2, Zhengjie Wang3

  • 1Department of Medical Cellular Biology and Genetics, Shanxi Medical University, Taiyuan, China.

Insights

MicroRNA-138-5p (miR-138-5p) is downregulated in colorectal carcinoma (CRC), suppressing tumor growth. Lower miR-138-5p levels correlate with poor prognosis, suggesting its potential as a therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • MicroRNA-138-5p (miR-138-5p) is implicated in various cancers, but its role in colorectal carcinoma (CRC) is unclear.
  • Understanding miR-138-5p's function is crucial for developing new CRC therapies.

Purpose of the Study:

  • To investigate the biological effects and clinical significance of miR-138-5p in colorectal carcinoma.
  • To elucidate the underlying molecular mechanisms of miR-138-5p in CRC progression.

Main Methods:

  • Quantitative real-time PCR to analyze miR-138-5p expression in CRC tissues and cell lines.
  • In vitro and in vivo assays (proliferation, colony formation, cell cycle, apoptosis) to assess miR-138-5p's effects on CRC growth.
  • Bioinformatic predictions and experimental validation to identify miR-138-5p targets.

Main Results:

  • miR-138-5p was significantly downregulated in CRC tissues and cell lines.
  • Lower miR-138-5p expression correlated with poor patient prognosis.
  • miR-138-5p suppressed CRC cell growth and promoted apoptosis in vitro and in vivo.
  • miR-138-5p directly targets MCU, inhibiting mitochondrial biogenesis and reducing ROS production in CRC.

Conclusions:

  • Downregulation of miR-138-5p promotes CRC growth by increasing MCU expression, mitochondrial biogenesis, and ROS production.
  • miR-138-5p acts as a tumor suppressor in CRC.
  • Targeting the miR-138-5p/MCU pathway offers a potential therapeutic strategy for colorectal carcinoma.

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...
3.0K
Electron Transport Chain: Complex I and II01:46

Electron Transport Chain: Complex I and II

The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
14.6K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
3.8K
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
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
3.7K