CircSMC3 regulates gastric cancer tumorigenesis by targeting miR-4720-3p/TJP1 axis

Tianfang Xia1, Zhenguo Pan2, Jie Zhang1

  • 1Department of General Surgery, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huaian City, Huaiyin District, Jiangsu Province, China.

Cancer Medicine
|April 22, 2020
PubMed

Insights

Circular RNAs (circRNAs) promote gastric cancer progression. This study identifies circSMC3 as a key player, driving cancer cell proliferation and motility via the circSMC3/miR-4720-3p/TJP1 pathway.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Circular RNAs (circRNAs) are increasingly recognized for their roles in human cancers.
  • The specific mechanisms of circRNA involvement in gastric cancer pathogenesis remain largely unknown.

Purpose of the Study:

  • To elucidate the molecular mechanisms by which circRNAs contribute to gastric cancer progression.
  • To identify specific circRNAs and their interaction pathways involved in gastric cancer.

Main Methods:

  • CircRNA microarray analysis to detect dysregulated circRNAs in gastric cancer tissues.
  • Kaplan-Meier survival analysis to correlate circRNA expression with patient survival.
  • Functional assays (e.g., knockdown) to assess the impact of circRNA on cell proliferation and motility.
  • MiRNA sponge assays and 3'UTR target validation to elucidate the molecular mechanism.

Main Results:

  • An upregulated circRNA, circSMC3 (hsa_circ_0000260), was identified in gastric cancer tissues.
  • High circSMC3 expression correlated with poor overall survival in gastric cancer patients.
  • Loss of circSMC3 function significantly inhibited gastric cancer cell proliferation and motility.
  • circSMC3 functions as a miRNA sponge for miR-4720-3p, leading to decreased miR-4720-3p levels.
  • Tight junction protein 1 (TJP1) was identified as a direct target of miR-4720-3p.

Conclusions:

  • CircSMC3 promotes gastric cancer cell proliferation and motility.
  • The circSMC3/miR-4720-3p/TJP1 axis is a key pathway in gastric cancer progression.
  • circSMC3 represents a potential therapeutic target for gastric cancer.

Related Concept Videos

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...
4.5K
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...
3.6K
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...
23.7K
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...
5.0K
The Tumor Microenvironment02:17

The Tumor Microenvironment

Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...
7.5K
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...
7.6K