CircRNA circ-ITCH suppresses papillary thyroid cancer progression through miR-22-3p/CBL/β-catenin pathway

Minnan Wang1, Bo Chen2, Zixuan Ru1

  • 1Department of Endocrinology and Metabolism, The Second Affiliated Hospital, Harbin Medical University, Harbin, 150086, Heilongjiang Province, China.

Insights

This study reveals that low levels of circular RNA circ-ITCH in papillary thyroid cancer (PTC) promote tumor growth. Restoring circ-ITCH suppresses cancer progression by inhibiting the circ-ITCH/miR-22-3p/CBL/β-catenin pathway.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Circular RNAs (circRNAs) are emerging regulators in carcinogenesis.
  • The specific role of circRNAs in papillary thyroid cancer (PTC) remains largely undefined.

Purpose of the Study:

  • To investigate the function of circRNA circ-ITCH in PTC development.
  • To elucidate the underlying molecular mechanisms of circ-ITCH in PTC.

Main Methods:

  • Quantitative real-time PCR to measure circ-ITCH expression.
  • In vitro gain-of-functional assays (cell proliferation, invasion, apoptosis).
  • In vivo tumor growth assays.
  • Bioinformatics analysis and luciferase reporter assays to identify miRNA targets and downstream pathways.

Main Results:

  • Circ-ITCH expression is significantly downregulated in PTC tissues compared to normal adjacent tissues.
  • Overexpression of circ-ITCH inhibits PTC cell proliferation and invasion, and promotes apoptosis in vitro.
  • Circ-ITCH overexpression impairs tumor growth in vivo.
  • Circ-ITCH acts as a sponge for miR-22-3p, upregulating CBL expression.
  • CBL upregulation suppresses the Wnt/β-catenin pathway, attenuating PTC progression.

Conclusions:

  • Circ-ITCH functions as a tumor suppressor in PTC.
  • A novel circ-ITCH/miR-22-3p/CBL/β-catenin signaling pathway is identified in PTC progression.
  • Circ-ITCH represents a potential therapeutic target for PTC.

Related Concept Videos

TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
10.5K
Catenins01:23

Catenins

Catenins are characterized by multiple binding domains and dynamic structures that allow them to function as linker proteins in cell junction complexes. All catenins, except α-catenin, contain a characteristic protein sequence called the armadillo repeat and are therefore also called armadillo proteins.
Catenins in Cell Junctions
Catenins bind to cell adhesion molecules such as cadherins and link them to different cytoskeletal proteins depending on the type of cell junction. At the...
3.1K
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...
4.8K
Papillary Dermis01:11

Papillary Dermis

Dermis
The dermis might be considered the "core" of the integumentary system, as distinct from the epidermis and hypodermis. It contains blood and lymph vessels, nerves, and other structures, such as hair follicles and sweat glands. The dermis is made of two layers of connective tissue that comprise an interconnected mesh of elastin and collagenous fibers, produced by fibroblasts.
Papillary Layer
The papillary layer is made of loose, areolar connective tissue, which means the collagen...
5.7K
The Thyroid Gland01:23

The Thyroid Gland

The thyroid gland is a small, butterfly-shaped gland located in the neck and covers the anterior surface of the trachea. The gland has two lateral lobes connected by a thin tissue mass called the isthmus. Internally, each lobe comprises many small spherical structures known as thyroid follicles, surrounded by a network of blood vessels.
The follicles have a central cavity lined by simple cuboidal to squamous epithelial cells called follicular cells. These cells produce the glycoprotein...
7.7K
C4 Pathway and CAM01:27

C4 Pathway and CAM

Most plants use the C3 pathway for carbon fixation. However, some plants, such as sugar cane, corn, and cacti that grow in hot conditions, use alternative pathways to fix carbon and conserve energy loss due to photorespiration. Photorespiration is the process that occurs when the oxygen concentration is high. Under such conditions, the rubisco enzyme in the Calvin cycle binds O2 instead of CO2, which halts photosynthesis and consumes energy.
C4 Pathway
The C4 pathway is used by plants such as...
49.2K