Hsa_circ_0008259 modulates miR-21-5p and PDCD4 expression to restrain osteosarcoma progression

Kai Guan1, Shizhang Liu2, Keke Duan2

  • 1The Second Department of Orthopaedics, The First People's Hospital of Xianyang, Xianyang 712000, Shaanxi Province, China.

Aging
|December 14, 2021
PubMed
Abstract

Insights

Circular RNA circ_0008259 inhibits osteosarcoma progression by regulating the miR-21-5p/PDCD4 axis. This finding offers new insights into osteosarcoma molecular mechanisms and potential therapeutic targets.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Osteosarcoma (OS) is a common pediatric bone cancer with poorly understood molecular mechanisms.
  • Circular RNAs (circRNAs) are increasingly recognized for their roles in cancer progression.
  • This study investigates the role of circ_0008259 in OS tumorigenesis.

Purpose of the Study:

  • To identify and characterize the function of circ_0008259 in osteosarcoma.
  • To elucidate the molecular mechanism by which circ_0008259 influences OS progression.
  • To explore the regulatory relationship between circ_0008259, miR-21-5p, and PDCD4 in OS.

Main Methods:

  • Differential expression analysis of circRNAs in OS tissues to identify circ_0008259.
  • Quantitative real-time PCR (qRT-PCR) to measure expression levels of circ_0008259, miR-21-5p, and PDCD4 mRNA.
  • In vitro assays including cell counting kit-8, Transwell, and flow cytometry to assess cell viability, metastasis, and apoptosis.
  • Bioinformatics analysis, dual-luciferase reporter assays, RNA-binding protein immunoprecipitation, and RNA-pull down assays to determine molecular interactions.
  • Western blot to detect protein expression levels.

Main Results:

  • Circ_0008259 and PDCD4 expression were downregulated, while miR-21-5p was upregulated in OS tissues and cells.
  • Overexpression of circ_0008259 significantly suppressed OS cell proliferation and metastasis while promoting apoptosis.
  • PDCD4 was confirmed as a target of miR-21-5p, and circ_0008259 competitively bound to miR-21-5p, thereby increasing PDCD4 expression in OS cells.

Conclusions:

  • Circ_0008259 functions as a tumor suppressor in osteosarcoma.
  • The circ_0008259/miR-21-5p/PDCD4 axis plays a critical role in regulating OS progression.
  • Targeting the circ_0008259/miR-21-5p/PDCD4 pathway may offer a novel therapeutic strategy for osteosarcoma.

Related Concept Videos

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
Hedgehog Signaling Pathway02:33

Hedgehog Signaling Pathway

The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
7.7K
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...
8.0K
Tumor Progression02:07

Tumor Progression

Tumor progression is a phenomenon where the pre-formed tumor acquires successive mutations to become clinically more aggressive and malignant. In the 1950s, Foulds first described the stepwise progression of cancer cells through successive stages.
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
6.6K
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...
3.2K