Silencing Transmembrane Protein 45B (TNEM45B) Inhibits Proliferation, Invasion, and Tumorigenesis in Osteosarcoma

Oncology Research
|March 1, 2017
PubMed

Insights

Transmembrane protein 45B (TMEM45B) is upregulated in osteosarcoma and drives cancer cell proliferation and migration. Inhibiting TMEM45B suppressed tumor growth, suggesting it acts as an oncogene.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Transmembrane protein 45B (TMEM45B) expression is altered in various human tumors.
  • The specific role of TMEM45B in osteosarcoma pathogenesis is not well understood.

Purpose of the Study:

  • To investigate the biological function of TMEM45B in osteosarcoma.
  • To determine if TMEM45B regulates osteosarcoma cell behavior and progression.

Main Methods:

  • Quantitative real-time PCR and Western blotting to assess TMEM45B expression.
  • In vitro cell assays (proliferation, migration, invasion) following TMEM45B knockdown.
  • In vivo tumor xenograft model in nude mice to evaluate TMEM45B's effect on tumor growth.
  • Analysis of Wnt/β-catenin signaling pathway components (β-catenin, cyclin D1, c-Myc).

Main Results:

  • TMEM45B expression was significantly upregulated at both protein and mRNA levels in osteosarcoma cell lines.
  • TMEM45B knockdown inhibited osteosarcoma cell proliferation, migration, and invasion in vitro.
  • Knockdown of TMEM45B led to decreased expression of β-catenin, cyclin D1, and c-Myc.
  • TMEM45B inhibition attenuated tumor growth in vivo.

Conclusions:

  • TMEM45B plays a crucial role in promoting osteosarcoma cell proliferation, migration, and invasion.
  • The oncogenic effects of TMEM45B in osteosarcoma are partially mediated through the Wnt/β-catenin signaling pathway.
  • TMEM45B is a potential oncogene and therapeutic target in osteosarcoma development and progression.

Related Concept Videos

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...
5.3K
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...
6.2K
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...
5.0K
Replicative Cell Senescence02:15

Replicative Cell Senescence

Replicative cell senescence is a property of cells that allows them to divide a finite number of times throughout the organism's lifespan while preventing excessive proliferation. Replicative senescence is associated with the gradual loss of the telomere — short, repetitive DNA sequences found at the end of the chromosomes. Telomeres are bound by a group of proteins to form a protective cap on the ends of chromosomes. Embryonic stem cells express telomerase — an enzyme that adds...
4.5K
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...
8.0K
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 the pre-miRNA...
4.2K