LncOCMRL1 promotes oral squamous cell carcinoma growth and metastasis via the RRM2/EMT pathway

Nan Lu1,2,3, Qiming Jiang1,3,4,5, Tianshu Xu1,3,4,6

  • 1Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, PR China.

Abstract

Insights

Oral squamous cell carcinoma metastasis-related lncRNA 1 (lncOCMRL1) promotes cancer growth and metastasis. Targeting lncOCMRL1 with nanoparticles effectively inhibits oral cancer progression and metastasis.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biotechnology

Background:

  • Long noncoding RNAs (lncRNAs) play roles in cancer, but their functions are often unknown.
  • Metastasis limits treatment outcomes in cancers like oral squamous cell carcinoma (OSCC).
  • Identifying key lncRNAs in OSCC metastasis is crucial for developing new therapies.

Purpose of the Study:

  • To investigate the role of oral squamous cell carcinoma metastasis-related lncRNA 1 (lncOCMRL1) in OSCC metastasis.
  • To elucidate the molecular mechanisms by which lncOCMRL1 promotes OSCC progression.
  • To develop a targeted nanodelivery system for lncOCMRL1-based therapy.

Main Methods:

  • Analyzed lncRNA expression profiles in OSCC tissues and cell lines.
  • Performed functional assays (Transwell, colony formation) to assess OSCC cell invasion, migration, and proliferation after lncOCMRL1 knockdown.
  • Utilized molecular techniques (RNA pull-down, mass spectrometry, RIP, WB) to explore the underlying mechanisms.
  • Developed and tested reduction-responsive nanoparticles for siRNA delivery.

Main Results:

  • lncOCMRL1 expression is elevated in metastatic OSCC tissues and cells.
  • High lncOCMRL1 expression promotes OSCC growth and metastasis in vitro and in vivo.
  • lncOCMRL1 induces epithelial-mesenchymal transition (EMT) by suppressing RRM2 ubiquitination, enhancing proliferation and metastasis.
  • Nanoparticle-mediated delivery of siRNA targeting lncOCMRL1 effectively inhibited OSCC tumor growth and metastasis in vivo.

Conclusions:

  • lncOCMRL1 is a key driver of OSCC metastasis.
  • lncOCMRL1 is a potential therapeutic target for blocking lymph node metastasis in OSCC.
  • Nanoparticle-based delivery of lncOCMRL1 siRNA shows promise for OSCC treatment.

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...
8.5K
Metastasis02:30

Metastasis

Metastasis is the spread of cancer cells from the original site to distant locations in the body. Cancer cells can spread via blood vessels (hematogenous) as well as lymph vessels in the body.
Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...
5.5K
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
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...
5.0K
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...
3.0K
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