MicroRNA Signature Linked to Rare Cause of Cushing’s

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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A clinical researcher views samples through a microscope in this illustration.

There are sets of microRNAs that may be used as markers for inherited or newly arising primary macronodular adrenal hyperplasia (PMAH), a rare cause of Cushing’s syndrome, a small study found.

According to researchers, these microRNAs — short RNA molecules that help control the activity of certain genes — also may play an important role in the development of the disease.

“Specific miRNAs, such as miR-17, miR-20a and miR-130b, may be new targets for further functional studies of PMAH,” they wrote.

The study, “MicroRNA expression signature and target prediction in familial and sporadic primary macronodular adrenal hyperplasia (PMAH),” was published in the journal BMC Endocrine Disorders by a team of researchers in China.

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Cushing’s syndrome occurs when there is too much cortisol in the body. Sometimes, this is caused by an excess of adrenocorticotropic hormone, which drives the adrenal glands atop the kidneys to produce cortisol.

Other times, the adrenal glands themselves become too big or too active. This is the case for people with PMAH, who grow multiple benign (non-cancerous) lumps in the adrenal glands. As a result, the adrenal glands become bigger and start producing higher-than-normal levels of cortisol. 

“PMAH accounts for fewer than 1% of cases of adrenocorticotropic hormone-independent Cushing’s syndrome, and the extent of cortisol excess ranges from subclinical to overt Cushing’s syndrome,” the researchers wrote.

While PMAH most commonly occurs sporadically, more rarely it can be associated with genetic mutations running in families. Researchers have previously used a technique called whole-genome sequencing to find out which mutations may be causing the disease in three members of a family.

Now, researchers sought to learn if microRNAs might be as useful for better describing PMAH, as they are for other diseases.

“We believe that the microRNA expression signature may provide additional information to supplement the whole-genome analysis previously performed in this set of patients,” they wrote.

The study included tissue samples from three patients with familial PMAH, two patients with sporadic PMAH, and three healthy individuals used as controls.

To understand if there was a signature unique to PMAH, researchers used a technique called microarray to look at which microRNAs were “on” or “off” in tissue samples from patients and controls.

They found significant differences in the expression, or activity, of 16 microRNAs between patients with familial PMAH and controls, and in the expression of eight microRNAs between those with sporadic PMAH and controls. Each of the two microRNA sets could be used to distinguish patients from controls.

There also was a set of 11 microRNAs that was found capable of distinguishing patients with familial PMAH from those with sporadic PMAH.

Many of these microRNAs were involved in important processes, including the circadian rhythm pathway that controls the body’s internal clock, cancer signaling pathways, and others. A signaling pathway is a series of chemical reactions in a cell, in which signals are passed from molecule to molecule in a concerted way to control a particular function.

Three of the microRNAs that were expressed more highly in tissue samples from patients versus controls included miR-17 and miR-20a. They all have been implicated in the death of cells induced by glucocorticoids. For this reason, researchers think they may play a role in the development of PMAH.

“Our findings contribute not only to an improved understanding of this benign disease but also to the development of new therapeutic and preventative strategies for PMAH,” they wrote.