MiR-9-1 Suppresses Cell Proliferation and Promotes Apoptosis by Targeting UHRF1 in Lung Cancer

Cheng-You Jia1, Wei Xiang2, Ji-Bin Liu3

  • 1Shanghai Tenth People's Hospital, 278245Tongji University School of Medicine, Shanghai, China.

Insights

MicroRNA-9 to 1 (miR-9 to 1) suppresses lung cancer growth by targeting UHRF1. This leads to cell cycle arrest and re-expression of tumor suppressors p15, p16, and p21, offering a new therapeutic strategy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Gene Regulation

Background:

  • Lung cancer remains a leading cause of cancer mortality globally.
  • MicroRNAs (miRNAs) play crucial roles in cellular processes, including cancer development.
  • Existing treatments for lung cancer have limitations, necessitating novel therapeutic approaches.

Purpose of the Study:

  • To investigate the role of microRNA-9 to 1 (miR-9 to 1) in lung cancer.
  • To identify the molecular targets of miR-9 to 1 involved in lung cancer suppression.
  • To elucidate the mechanism by which miR-9 to 1 inhibits lung cancer progression.

Main Methods:

  • Overexpression of miR-9 to 1 in lung cancer cell lines (A549).
  • Assessment of cell proliferation, colony formation in vitro, and tumorigenicity in vivo.
  • Identification of UHRF1 as a direct target of miR-9 to 1 using molecular assays.
  • Analysis of cell cycle regulators (p15, p16, p21) at mRNA and protein levels.

Main Results:

  • Overexpression of miR-9 to 1 significantly suppressed lung cancer cell proliferation, colony formation, and tumorigenicity.
  • Ubiquitin-like containing PHD and RING finger domains 1 (UHRF1) was identified as a direct target of miR-9 to 1.
  • miR-9 to 1-mediated inhibition of UHRF1 led to G1 cell cycle arrest.
  • Re-expression of tumor suppressor genes p15, p16, and p21 was observed at both mRNA and protein levels in the miR-9 to 1 group.

Conclusions:

  • miR-9 to 1 acts as a tumor suppressor in lung cancer by targeting UHRF1.
  • The miR-9 to 1/UHRF1 axis regulates cell proliferation through the re-expression of p15, p16, and p21.
  • UHRF1 represents a novel therapeutic target for miR-9 to 1-based 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 ends...
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...
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...
Loss of Tumor Suppressor Gene Functions01:12

Loss of Tumor Suppressor Gene Functions

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against specific...
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...