miR-203a regulates proliferation, migration, and apoptosis by targeting glycogen synthase kinase-3β in human renal

Guanghui Hu1, Peng Lai, Min Liu

  • 1Department of Urology, Shanghai Tenth People's Hospital, Tongji University, 301 Yanchang Road, Shanghai, 200072, China, dhguanghui@gmail.com.

Insights

MicroRNA 203a (miR-203a) is overexpressed in renal cell carcinoma, contrary to its tumor-suppressive role elsewhere. High miR-203a levels correlate with advanced cancer stages and poorer survival, indicating it promotes kidney cancer progression.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • MicroRNAs (miRNAs) are key regulators of gene expression involved in cancer.
  • miR-203a is recognized as a tumor suppressor in many cancer types.
  • The specific role of miR-203a in renal cell carcinoma (RCC) remains unclear.

Purpose of the Study:

  • To investigate the expression levels of miR-203a in RCC tissues and cells.
  • To determine the correlation between miR-203a expression and clinical features in RCC patients.
  • To elucidate the functional role of miR-203a in RCC progression.

Main Methods:

  • Quantitative real-time PCR was used to measure miR-203a expression in RCC tissues and cell lines.
  • Bioinformatics analysis and luciferase reporter assays were employed to identify miR-203a targets.
  • In vitro experiments, including cell proliferation, migration, cell cycle, and apoptosis assays, were performed after miR-203a silencing.

Main Results:

  • miR-203a was found to be overexpressed in RCC tissues and cells compared to normal controls.
  • High miR-203a expression significantly correlated with advanced tumor stage and reduced overall survival.
  • Glycogen synthase kinase-3β (GSK-3β) was validated as a direct target of miR-203a.
  • Silencing miR-203a inhibited RCC cell proliferation and migration, induced G1 phase arrest, and promoted apoptosis.

Conclusions:

  • Contrary to its known function in other cancers, miR-203a acts as an oncomiR in renal cell carcinoma.
  • Overexpression of miR-203a promotes RCC progression and is associated with a poor prognosis.
  • Targeting miR-203a may represent a potential therapeutic strategy for renal cell carcinoma.

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...
3.6K
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...
5.1K
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...
4.0K
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
32.1K
The Retinoblastoma Gene01:20

The Retinoblastoma Gene

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.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
3.7K
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...
7.3K