MicroRNA Molecule May Regulate Mesothelioma

Gene Therapy

A team of international researchers recently identified a microRNA molecule — found within a gene common to mesothelioma — with the ability to control metastasis.

Malignant pleural mesothelioma (MPM) cells contain high levels of mesothelin, a protein biomarker overexpressed in several forms of cancer. Mesothelin is believed to be a key factor in how quickly mesothelioma metastasizes.

Researchers at the Royal College of Surgeons in Ireland discovered the single microRNA molecule miR-21-5p lowered levels of mesothelin, giving scientists a new lead to study, according to the findings published Jan. 26 in the journal PLOS One.

Although there is still much to learn, the discovery is another important advancement in mesothelioma research. It also could have a potential impact on gene therapy, an experimental procedure that targets the cancer at the molecular level through the manipulation of a patient’s genes.

“Theoretically, the administration of a ‘supplement’ of miR-21 could help in lowering the levels and perhaps this could help in combination with other therapies to slow the disease,” Stefano Landi, a professor at the University of Pisa in Italy and one of the authors of the study, told Asbestos.com.

MiR-21 Is ‘Poorly Investigated’ in Mesothelioma

For many years, scientists have analyzed different mircroRNAs and their roles in gene expression and post-transcriptional regulation.

The miR-21 molecule is considered a predictive biomarker for several types of aggressive cancers.

A 2014 study confirmed miR-21 is overexpressed in advanced rectal cancer tumors and may be directly involved with poor response to neoadjuvant chemoradiotherapy (nCRT), one of the common treatments of rectal cancer.

Mesothelin is overexpressed in all pancreatic cancers and mesotheliomas, and in more than 70 percent of colorectal, ovarian and non-small cell lung cancers.

While mesothelin regulates cell proliferation and invasiveness, the mechanisms for the gene’s overexpression in malignant tumors have yet to be clearly explained.

The study published in PLOS One is the latest to investigate miR-21 as a potential regulator of mesothelin, but it is one of few to research the microRNA’s role in the formation of pleural mesothelioma.

“Although it has been extensively studied in cancer, miR-21-5p has been poorly investigated in MPM,” lead author Chiara De Santi wrote in the study. “Here, miR-21-5p appears to act as a tumor suppressor [microRNA] since it negatively regulated an oncogene [mesothelin], and this could be explained considering that [microRNAs] could play different roles depending on the pattern of their target mRNAs expressed in that specific cancer type or tissue.”

Role of Gene Expression in Mesothelioma Diagnosis

While mesothelioma is incurable, oncologists and researchers agree the key to longer survival is early diagnosis.

More treatment options are available in the early stages of pleural mesothelioma. However, the cancer is often misdiagnosed as lung cancer or a less serious illness.

Mesothelioma cells grow and spread quickly following a decades-long latency period. By the time many diagnoses occur, mesothelioma has progressed to stage III or stage IV, where surgery or other treatments may no longer be an option.

Novel diagnostic tools such as the miRview meso test make it easier for doctors to differentiate between pleural mesothelioma and other forms of metastatic carcinomas. The test measures the expression levels of three specific biomarkers.

With continued research, miR-21 could prove to be another predictive biomarker for pleural mesothelioma.

Landi noted there are other strategies to lowering levels of mesothelin, including targeting the gene using MORAb-009 (amatuximab), a chimeric antibody. BAY 94-9343 (anetuman ravtansine) also shows an ability to kill cancer cells that overexpress mesothelin.

The CRS-27 vaccine fortifies a patient’s immune system to attack mesothelin.

Landi also said his team’s most recent study regarding miR-21 requires more investigation.

“We are doing basic research,” Landi said. “We do not expect to have immediate impact on the clinics.”


Matt Mauney is an award-winning journalist with nearly a decade of professional writing experience. He joined Asbestos.com in 2016, and he spends much of his time reading, analyzing and reporting on mesothelioma research articles to ensure people in the mesothelioma community know the latest medical advancements. Prior to joining Asbestos.com, Matt was a reporter at the Orlando Sentinel.

  1. De Santi, C. et al. (2017, January 26). Identification of MiR-21-5p as a Functional Regulator of Mesothelin Expression Using MicroRNA Capture Affinity Coupled with Next Generation Sequencing. Retrieved from http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0170999
  2. Lopes-Ramos, C. et al. (2014, November 28). Overexpression of miR-21-5p as a predictive marker for complete tumor regression to neoadjuvant chemoradiotherapy in rectal cancer patients. Retrieved from https://bmcmedgenomics.biomedcentral.com/articles/10.1186/s12920-014-0068-7
  3. Raffit, H. et al. (2007, December 19). Preclinical evaluation of MORAb-009, a chimeric antibody targeting tumor-associated mesothelin. Retrieved from https://www.researchgate.net/publication/5760880_Preclinical_evaluation_of_MORAb-009_a_chimeric_antibody_targeting_tumor-associated_mesothelin

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