RAB9A Plays an Oncogenic Role in Human Liver Cancer Cells

Pengfei Sun1, Lei Li1, Zhongchao Li1

  • 1Hepatobiliary and Pancreatic Surgery, Shandong Cancer Hospital and Institute, Shandong Fist Medical University and Shandong Academy of Medical Sciences, No. 440 Jiyan Road, Huaiyin District, Jinan City, 250117 Shandong Province, China.

Abstract

Insights

RAB9A promotes liver cancer growth by enhancing cell proliferation and invasion. This protein activates AKT signaling pathways, suggesting RAB9A as a potential therapeutic target for liver cancer.

Area of Science:

  • Molecular Biology
  • Oncology

Background:

  • RAB9A, a Rab GTPase, facilitates mannose-6-phosphate receptor transport.
  • The role of RAB9A in liver cancer remains largely uncharacterized.

Purpose of the Study:

  • To investigate the function of RAB9A in human liver cancer.
  • To elucidate the underlying molecular mechanisms of RAB9A's role in liver cancer progression.

Main Methods:

  • RAB9A expression was modulated using pcDNA3.1 plasmid and shRNA in Hep3b and HepG2 cells.
  • Cell proliferation, apoptosis, invasion, and migration were assessed using CCK-8, colony formation, apoptosis analysis, transwell, and wound healing assays.
  • Western blot analysis and pathway inhibition (BEZ235) were employed to study mechanisms.

Main Results:

  • RAB9A overexpression enhanced proliferation, clonality, invasion, and migration in liver cancer cells.
  • RAB9A inhibited apoptosis and mitochondrial apoptotic pathway activation.
  • RAB9A activated the AKT/mTOR signaling pathway, and its inhibition partially reversed RAB9A's oncogenic effects.

Conclusions:

  • RAB9A exhibits a carcinogenic role in human liver cancer progression.
  • The AKT signaling pathway is partially involved in RAB9A-mediated liver cancer.
  • RAB9A represents a potential therapeutic target for liver cancer treatment.

Related Concept Videos

Rous Sarcoma Virus (RSV) and Cancer01:03

Rous Sarcoma Virus (RSV) and Cancer

Rous Sarcoma virus or RSV was discovered by F. Peyton Rous in the year 1911 as a filterable transmissible agent that could cause tumors in chickens. He won a Nobel Prize for this discovery in 1966. His experiments clearly demonstrated that some cancers could be caused by infectious agents and led to the discovery of many more cancer-causing viruses in animals as well as humans.
RSV is a retrovirus that contains two copies of a plus-strand  RNA genome. Its genome consists of four main open...
6.0K
The Ras Gene02:38

The Ras Gene

The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a...
6.9K
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 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,...
4.6K
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
Mechanisms of Retrovirus-induced Cancers01:51

Mechanisms of Retrovirus-induced Cancers

Retroviruses are RNA viruses that have been shown to cause cancers in diverse species, including chickens, mice, cats, and monkeys. The RNA genomes of these viruses are first reverse-transcribed into single and then double-stranded DNA (dsDNA) copies. This dsDNA called proviral DNA then integrates into the host genome. Subsequently, the host cell transcribes the proviral DNA in concert with the chromosomal DNA. This leads to the production of viral RNA and proteins that assemble at the host...
6.7K