MicroRNA-145 inhibits cell proliferation by directly targeting ADAM17 in hepatocellular carcinoma

Yuwu Liu1, Chang Wu2, Ying Wang1

  • 1Department of Pathology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.

Oncology Reports
|September 2, 2014
PubMed

Insights

MicroRNA-145 (miR-145) suppresses liver cancer growth by targeting ADAM17. This finding highlights miR-145 as a potential therapeutic target for hepatocellular carcinoma.

Area of Science:

  • Molecular Biology
  • Oncology
  • Gene Regulation

Background:

  • MicroRNAs (miRNAs) are crucial regulators of cellular processes.
  • Emerging evidence links miRNAs to cancer development, but their precise roles in tumorigenesis remain unclear.
  • Understanding miRNA-mediated regulatory mechanisms is vital for cancer research.

Purpose of the Study:

  • To investigate the role of miR-145 in liver cancer.
  • To identify the direct targets of miR-145 in hepatocellular carcinoma cells.
  • To elucidate the molecular mechanisms by which miR-145 affects cancer cell proliferation.

Main Methods:

  • Quantitative real-time PCR and Western blotting to measure mRNA and protein levels.
  • Dual luciferase reporter assays to confirm direct miRNA-target interactions.
  • Cell proliferation and growth assays in liver cancer cell lines (SMMC-7721, BEL-7402, Huh-7).

Main Results:

  • miR-145 significantly reduced mRNA and protein expression of A disintegrin and metalloproteinase 17 (ADAM17) in liver cancer cells.
  • ADAM17 was confirmed as a direct target of miR-145.
  • miR-145 inhibited proliferation and growth activity in SMMC-7721 cells, suggesting tumor suppressor functions.
  • Silencing ADAM17 also decreased proliferation and growth activity, and reduced MMP-9 expression.

Conclusions:

  • miR-145 inhibits liver cancer cell proliferation by directly targeting ADAM17.
  • This interaction suggests miR-145 plays a tumor-suppressive role in hepatocellular carcinoma.
  • miR-145 represents a promising therapeutic target for hepatocellular carcinoma 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 the pre-miRNA...
3.0K
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...
20.8K
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
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
Experimental RNAi02:15

Experimental RNAi

RNA interference (RNAi) is a cellular mechanism that inhibits gene expression by suppressing its transcription or activating the RNA degradation process. The mechanism was discovered by Andrew Fire and Craig Mello in 1998 in plants. Today, it is observed in almost all eukaryotes, including protozoa, flies, nematodes, insects, parasites, and mammals. This precise cellular mechanism of gene silencing has been developed into a technique that provides an efficient way to identify and determine the...
6.5K