Pathology and Diseases

KRT7 Gene: Its Function and Its Link to Cancer

Explore the KRT7 gene, from its essential role in maintaining cell structure to how its activity levels provide key insights into health and disease.

The human body’s DNA holds the blueprint for building and operating an organism. Within this DNA, specific sections called genes provide the code for creating proteins. Proteins are the workhorses of the cell, carrying out a vast array of functions. The KRT7 gene is one such segment, holding instructions for a protein involved in cellular architecture that has become a subject of study in various health conditions.

Genes, Proteins, and the Keratin Family

Every cell relies on genes to produce the proteins necessary for life. A gene is a recipe in DNA that a cell transcribes into messenger RNA (mRNA). This mRNA molecule travels from the cell’s nucleus to ribosomes, which translate the code to assemble a specific protein. This process turns genetic information into the functional machinery that drives cellular activities.

Among the thousands of proteins, one large group is the keratin family. Keratins are fibrous structural proteins whose primary job is to provide strength and resilience to cells, and they are the main components of hair, skin, and nails. Within cells, keratins assemble into networks of intermediate filaments that act as an internal scaffold. This network helps the cell maintain its shape, withstand physical stress, and connect to neighboring cells to form cohesive tissues.

The keratin family is diverse, with over 50 different types in humans, each expressed in specific cells. They are divided into two categories, Type I and Type II, based on their chemical properties. To form the strong filament network, at least one Type I keratin must pair with one Type II keratin. This specific pairing allows for the creation of various keratin structures tailored to the needs of different tissues.

The KRT7 Gene and Its Protein Product

The KRT7 gene codes for Keratin 7, a Type II keratin protein. Unlike the keratins in the outer layers of the skin, Keratin 7 is found in the simple epithelia. These are single-layer cell tissues that line internal organs, glands, and body cavities. Keratin 7 is a common feature in the epithelial cells of the lungs, breast tissue, and ducts within glands.

In these locations, Keratin 7 performs its duty of maintaining cellular structure. It partners with a Type I keratin, most commonly Keratin 19, to form an intermediate filament network that provides mechanical support. This framework is important for tissue integrity, helping it resist stretching and compression. This role ensures these delicate linings can perform their functions, such as secretion, absorption, and protection.

The expression of Keratin 7 is highly specific, as it is produced in certain cell types but not others. For example, it is not found in the epithelial cells of the colon or prostate. This tissue-specific expression pattern is a characteristic used to identify the origin of cells.

How KRT7 Gene Expression is Controlled

Gene expression, the process of turning a gene “on” or “off” to produce a protein, must be carefully controlled. This regulation ensures that each cell produces the right proteins at the right time and in the right amounts. One control method involves molecules that can interfere with the protein-building instructions.

The KRT7 gene’s expression is influenced by an antisense RNA. A long non-coding RNA called KRT7 antisense RNA 1 (KRT7-AS1) performs this regulatory role. Unlike the KRT7 mRNA, KRT7-AS1 does not code for a protein; its function is to manage the KRT7 gene’s activity.

KRT7-AS1 works by binding to the KRT7 mRNA molecule, creating a double-stranded RNA structure. This interaction can have different outcomes. It can mark the KRT7 mRNA for destruction, reducing the gene’s expression, or it can stabilize the mRNA, leading to increased protein production. Disruptions in this regulatory balance can have significant consequences.

KRT7’s Link to Cancer

Disruptions in the regulated expression of KRT7 and its regulator, KRT7-AS1, are notable in cancer. In many types of cancer, such as those of the ovary, pancreas, and lung, the levels of Keratin 7 protein are abnormally high. Because of this strong association, KRT7 is widely used by pathologists as a biomarker to help diagnose certain cancers and distinguish between different cancer types.

Altered KRT7 expression is also involved in disease progression, and high levels are often linked to a poorer prognosis. An excess of Keratin 7 can contribute to processes that make cancer more aggressive. For example, it is implicated in promoting the epithelial-mesenchymal transition (EMT), a process where cancer cells become more mobile, enabling them to metastasize to other parts of the body.

The relationship with cancer involves its regulatory partner, KRT7-AS1. In some cancers, like those of the lung and breast, low KRT7-AS1 levels may lead to an overproduction of the cancer-promoting KRT7 protein. In these contexts, KRT7-AS1 appears to act as a tumor suppressor, making the KRT7 pathway a target for new cancer therapies aimed at inhibiting tumor growth.

KRT7’s Connection to Other Medical Conditions

KRT7’s influence extends beyond cancer, as altered expression is linked to conditions involving inflammation. A connection has been found between KRT7 and inflammatory bowel diseases (IBD), disorders that cause chronic inflammation of the digestive tract. The protein’s specific function in this context is still under investigation.

KRT7 expression is also linked to how tumors interact with the immune system. In some cancers, like pancreatic adenocarcinoma, KRT7 levels correlate with the infiltration of immune cells into the tumor microenvironment. This suggests KRT7 may modulate the body’s immune response, potentially making the tumor harder for immune cells to attack.

This immune system interaction has implications for cancer treatment, as high KRT7 expression has been associated with resistance to certain drugs. This shows KRT7 is not merely a structural component but a dynamic player whose balance is important for maintaining tissue health.

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