MicroRNA-31-5p modulates cell cycle by targeting human mutL homolog 1 in human cancer cells

Zhiwei Zhong1, Zhuo Dong, Lihua Yang

  • 1Institute of Biochemistry and Molecular Biology, School of Medicine, Ningbo University, 818 Fenghua Road, Ningbo, China.

Insights

MicroRNAs (miRNAs) regulate cell cycle in lung cancer by targeting the hMLH1 DNA repair gene. Targeting miR-31-5p offers a potential new therapy for non-small cell lung cancer (NSCLC).

Area of Science:

  • Molecular Biology
  • Oncology
  • Genetics

Background:

  • MicroRNAs (miRNAs) and DNA mismatch repair (MMR) genes, including human mutL homolog 1 (hMLH1), are implicated in human cancer progression.
  • The specific roles of miRNAs in regulating MMR genes and their impact on the cell cycle in lung cancer remain unclear.

Purpose of the Study:

  • To investigate the regulatory role of miR-31-5p in human mutL homolog 1 (hMLH1) gene expression.
  • To determine the effect of miR-31-5p on the cell cycle in non-small cell lung cancer (NSCLC).

Main Methods:

  • Analysis of miR-31-5p and hMLH1 expression correlation in NSCLC cell lines.
  • Experimental manipulation (knockdown and overexpression) of miR-31-5p and hMLH1.
  • Cell cycle phase analysis (G2/M and S phase arrest) using flow cytometry.
  • Western blot analysis to assess protein expression levels.

Main Results:

  • miR-31-5p expression was inversely correlated with hMLH1 expression in NSCLC cells, with hMLH1 identified as a direct target.
  • miR-31-5p knockdown led to G2/M phase arrest and increased hMLH1 protein levels.
  • miR-31-5p overexpression resulted in S phase arrest and decreased hMLH1 protein levels.
  • hMLH1 knockdown upregulated miR-31-5p and induced S phase arrest.

Conclusions:

  • miR-31-5p modulates the cell cycle in NSCLC by post-transcriptionally targeting hMLH1.
  • This miR-31-5p/hMLH1 interaction represents a potential novel therapeutic strategy for lung cancer treatment.

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...
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...
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
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...
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...