Hsa_circ_0004712 downregulation attenuates ovarian cancer malignant development by targeting the miR-331-3p/FZD4

Xuan Zhou1, Jinchi Jiang2, Shuaishuai Guo3

  • 1Reproductive Medicine Center, Shenyang Women's and Children's Hospital, No. 87 Danan Street, Shenhe District, Shenyang, 110000, Liaoning, China.

Journal of Ovarian Research
|September 11, 2021
PubMed
Abstract

Insights

Circular RNAs (circRNAs) like hsa_circ_0004712 are involved in ovarian cancer (OC). This study found hsa_circ_0004712 promotes OC by regulating the miR-331-3p/FZD4 pathway, suggesting it as a potential biomarker.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Circular RNAs (circRNAs) are increasingly recognized for their role in various cancers, including ovarian cancer (OC).
  • Understanding the specific functions of individual circRNAs, such as hsa_circ_0004712, is crucial for developing targeted therapies.
  • This study investigates the mechanism of hsa_circ_0004712 in the context of OC development.

Purpose of the Study:

  • To elucidate the functional role of hsa_circ_0004712 in ovarian cancer.
  • To explore the molecular mechanism underlying the action of hsa_circ_0004712 in OC.
  • To assess the potential of hsa_circ_0004712 as a diagnostic and therapeutic target for OC.

Main Methods:

  • Quantitative real-time PCR to assess hsa_circ_0004712 expression levels in OC tissues and cells.
  • In vitro assays (proliferation, colony formation, invasion, migration, apoptosis) to evaluate the functional impact of hsa_circ_0004712.
  • In vivo tumor xenograft models to confirm the role of hsa_circ_0004712 in tumor development.
  • Luciferase reporter assays and Western blotting to confirm targeting relationships between hsa_circ_0004712, miR-331-3p, and FZD4.

Main Results:

  • hsa_circ_0004712 was significantly overexpressed in OC tissues and cell lines.
  • Downregulation of hsa_circ_0004712 suppressed OC cell proliferation, migration, invasion, and promoted apoptosis.
  • hsa_circ_0004712 acts as a sponge for miR-331-3p, leading to increased FZD4 expression, and this pathway was validated both in vitro and in vivo.

Conclusions:

  • hsa_circ_0004712 promotes ovarian cancer progression by regulating the miR-331-3p/FZD4 axis.
  • Inhibition of hsa_circ_0004712 demonstrates anti-tumor effects in OC models.
  • hsa_circ_0004712 represents a potential biomarker for OC diagnosis and a therapeutic target.

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...
3.3K
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...
4.7K
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...
3.9K
Cancer-Critical Genes II: Tumor Suppressor Genes01:05

Cancer-Critical Genes II: Tumor Suppressor Genes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
8.4K
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...
5.3K
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR...
2.3K