miR-145 functions as tumor suppressor and targets two oncogenes, ANGPT2 and NEDD9, in renal cell carcinoma

Ruijing Lu1, Ziliang Ji, Xiaoqing Li

  • 1Department of Clinical Laboratory, Peking University Shenzhen Hospital, Shenzhen, 518036, China.

Abstract

Insights

MicroRNA-145 (miR-145) acts as a tumor suppressor in renal cell carcinoma (RCC). Restoring miR-145 inhibits RCC cell growth, migration, and invasion, offering a potential therapeutic target for this cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Aberrant microRNA (miRNA) expression is implicated in human cancer development.
  • Renal cell carcinoma (RCC) is a significant malignancy with complex molecular underpinnings.
  • Identifying novel tumor suppressors is crucial for understanding RCC pathogenesis and developing targeted therapies.

Purpose of the Study:

  • To identify a novel tumor suppressor miRNA in renal cell carcinoma (RCC).
  • To elucidate the physiological function and molecular mechanisms of miR-145 in RCC.
  • To evaluate miR-145 as a potential therapeutic target for RCC.

Main Methods:

  • Quantitative RT-PCR was used to assess miR-145 expression in RCC and adjacent normal tissues.
  • In vitro assays (proliferation, migration, invasion, apoptosis, cell cycle) were performed to determine miR-145 function.
  • Luciferase reporter assays identified direct targets of miR-145, including oncogenes ANGPT2 and NEDD9.
  • RT(2) Profiler EMT PCR array analyzed the impact of miR-145 on epithelial-to-mesenchymal transition (EMT)-related genes.

Main Results:

  • miR-145 expression was significantly downregulated in RCC tissues compared to normal adjacent tissues.
  • Restoration of miR-145 suppressed RCC cell proliferation, migration, and invasion.
  • miR-145 induced apoptosis and G2-phase cell cycle arrest in RCC cell lines.
  • miR-145 targets oncogenes ANGPT2 and NEDD9 and regulates multiple EMT-associated genes.

Conclusions:

  • miR-145 functions as a tumor suppressor in renal cell carcinoma.
  • The findings suggest that miR-145 holds potential as a therapeutic target for RCC treatment.

Related Concept Videos

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...
21.1K
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...
3.0K
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
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
lncRNA - Long Non-coding RNAs02:39

lncRNA - Long Non-coding RNAs

In humans, more than 80% of the genome gets transcribed. However, only around 2% of the genome codes for proteins. The remaining part produces non-coding RNAs which includes ribosomal RNAs, transfer RNAs, telomerase RNAs, and regulatory RNAs, among other types. A large number of regulatory non-coding RNAs have been classified into two groups depending upon their length – small non-coding RNAs, such as microRNA, which are less than 200 nucleotides in length, and long non-coding RNA...
7.5K
Loss of Tumor Suppressor Gene Functions01:12

Loss of Tumor Suppressor Gene Functions

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.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
4.9K