Low expression of long non-coding RNA ARAP1-AS1 can inhibit lung cancer proliferation by inducing G0/G1 cell cycle

Xinlu Tao1,2, Yan Zhang2, Jiaping Li2

  • 1Department of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China.

Abstract

Insights

Long non-coding RNA ARAP1-AS1 is highly expressed in lung cancer. Inhibiting ARAP1-AS1 significantly reduces lung cancer cell proliferation and growth, offering potential therapeutic targets.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Lung cancer is a leading cause of cancer-related mortality worldwide.
  • Long non-coding RNAs (lncRNAs) are emerging as critical regulators in various cancers, including lung cancer.
  • The specific role and molecular mechanisms of lncRNA ARAP1 antisense RNA 1 (ARAP1-AS1) in lung cancer remain largely unclear.

Purpose of the Study:

  • To investigate the expression and function of lncRNA ARAP1-AS1 in lung cancer.
  • To elucidate the molecular mechanism by which ARAP1-AS1 influences lung cancer development.
  • To evaluate ARAP1-AS1 as a potential molecular target for lung cancer diagnosis and therapy.

Main Methods:

  • Quantitative real-time PCR to assess ARAP1-AS1 expression in lung cancer tissues and cell lines.
  • Cell proliferation assays (MTT, plate cloning) and flow cytometry to evaluate the impact of ARAP1-AS1 knockdown on cell cycle progression.
  • Western blotting to analyze the expression of cell cycle-related proteins (cyclin D1, CDK4, CDK6).
  • Nude mouse xenograft models to assess the in vivo effect of ARAP1-AS1 knockdown on tumor growth.

Main Results:

  • ARAP1-AS1 was found to be significantly upregulated in lung cancer tissues and cell lines.
  • Knockdown of ARAP1-AS1 markedly inhibited lung cancer cell proliferation and colony formation in vitro.
  • ARAP1-AS1 knockdown induced G0/G1 phase cell cycle arrest and reduced cyclin D1 expression.
  • In vivo studies demonstrated that ARAP1-AS1 knockdown suppressed tumor growth and decreased Ki-67 expression in tumor tissues.

Conclusions:

  • LncRNA ARAP1-AS1 is oncogenic and overexpressed in lung cancer.
  • Downregulation of ARAP1-AS1 inhibits lung cancer cell proliferation and tumor growth both in vitro and in vivo.
  • ARAP1-AS1 may promote lung cancer progression by regulating the cell cycle, specifically through cyclin D1 inhibition.

Related Concept Videos

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...
9.4K
lncRNA - Long Non-coding RNAs02:39

lncRNA - Long Non-coding RNAs

3.1K
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...
6.8K
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...
4.9K
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
37.5K
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...
3.4K