KIAA1429 regulates lung adenocarcinoma proliferation and metastasis through the PI3K/AKT pathway by modulating

Wei Guo1,2, Tan Wang3, Qilin Huai1

  • 1Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Thoracic Cancer
|May 8, 2024
PubMed
Abstract

Insights

KIAA1429 regulates lung adenocarcinoma (LUAD) by affecting N6-methyladenosine (m6A) RNA levels. Suppressing KIAA1429 reduces m6A, stabilizes ARHGAP30, and inhibits tumor growth and metastasis.

Area of Science:

  • Epigenetics and Cancer Biology
  • RNA Modifications
  • Molecular Oncology

Background:

  • Epigenetic alterations are key drivers of cancer development.
  • N6-methyladenosine (m6A) RNA modification regulates gene expression and cellular fate.
  • The role of KIAA1429 (VIRMA) in lung adenocarcinoma (LUAD) remains largely undefined.

Purpose of the Study:

  • To investigate the role of KIAA1429 in the development of lung adenocarcinoma.
  • To elucidate the molecular mechanisms by which KIAA1429 influences LUAD progression.

Main Methods:

  • In vitro functional assays in LUAD cell lines.
  • Transcriptome sequencing to analyze gene expression profiles.
  • Methylation RNA immunoprecipitation sequencing (MeRIP-seq) to identify m6A-modified sites.
  • RNA stability assays to determine mRNA half-life.

Main Results:

  • KIAA1429 expression levels significantly impact LUAD cell proliferation and metastasis.
  • Transcriptome and MeRIP-seq analyses identified KIAA1429-regulated m6A modification targets.
  • KIAA1429 directly regulates ARHGAP30 expression by modulating its m6A levels.
  • Downregulation of KIAA1429 leads to decreased ARHGAP30 m6A, increased mRNA stability and expression, thereby inhibiting tumor proliferation and metastasis.

Conclusions:

  • KIAA1429 plays a critical role in LUAD tumorigenesis through m6A RNA modification.
  • Understanding KIAA1429's mechanism offers potential for novel molecular-based LUAD therapies.

Related Concept Videos

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...
3.5K
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...
3.8K
Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
2.6K
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...
4.5K
Tumor Progression02:07

Tumor Progression

Tumor progression is a phenomenon where the pre-formed tumor acquires successive mutations to become clinically more aggressive and malignant. In the 1950s, Foulds first described the stepwise progression of cancer cells through successive stages.
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
6.3K
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...
6.2K