Hsa_circ_0020378 targets miR-556-5p/MAPK1 to regulate osteosarcoma cell proliferation and migration

Zi Li1, Lei Zheng2, Liang Yang3

  • 1Department of Orthopedics & Plastic surgery, The Sixth Hospital of Wuhan, Affiliated Hospital of Jianghan University, Wuhan 430015, Hubei, PR China.

Gene
|December 26, 2022
PubMed

Insights

Circular RNA circ_0020378 promotes osteosarcoma (OS) growth by regulating the miR-556-5p/MAPK1 pathway. This finding suggests circ_0020378 as a potential therapeutic target for osteosarcoma intervention.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Osteosarcoma (OS) is a primary bone cancer threatening children's lives.
  • Circular RNAs (circRNAs) are increasingly recognized for their roles in OS malignancy.

Purpose of the Study:

  • To investigate the pathological role of the novel circ_0020378 in osteosarcoma progression.
  • To elucidate the underlying molecular mechanism involving the miR-556-5p/MAPK1 axis.

Main Methods:

  • Expression analysis of circ_0020378, miR-556-5p, and MAPK1 using RT-qPCR and Western blotting.
  • In vitro assays (CCK8, colony formation, Transwell) to assess cell proliferation and migration.
  • In vivo tumor xenograft model to evaluate tumor growth.
  • Luciferase reporter and RIP assays to confirm molecular interactions.

Main Results:

  • Circ_0020378 and MAPK1 were upregulated, while miR-556-5p was downregulated in OS tissues and cells.
  • Silencing circ_0020378 inhibited OS cell proliferation, migration, and tumor growth.
  • Circ_0020378 targeted miR-556-5p, which in turn targeted MAPK1.
  • The circ_0020378/miR-556-5p/MAPK1 axis promoted OS cell malignant behaviors.

Conclusions:

  • Circ_0020378 acts as a tumor promoter in osteosarcoma.
  • The circ_0020378/miR-556-5p/MAPK1 pathway is a critical regulator of OS progression.
  • This pathway represents a potential novel therapeutic target for osteosarcoma intervention.

Related Concept Videos

MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
5.8K
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...
4.6K
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
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
3.8K
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
6.4K
Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
2.7K