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Gene & Protein in Disease MOR in cancer

exert analgesic effect through different targets and
mechanisms.
2.3. Tumor

MOR can be expressed in many different cancer cells,
including BC , non-small cell lung cancer (NSCLC) ,
[70]
[69]
[71]
CRC , and hepatocellular carcinoma (HCC) [56,72] . In 1989,
[73]
Scopsi et al. was the first to propose that endogenous
opioid peptides may be related to cancer progression.
Thereafter, many reports have indicated that the activation
of MOR may be involved in malignant progression of
tumors, which is supported by the evidence that MOR
may affect the growth of CRC cells and the prognosis
[71]
of patients with liver and laryngeal cancer (Figure 3) [55,56] .
Therefore, MOR may be used as a new biomarker for
tumors and concerned as a new target in cancer treatment.
MOR expression level appears to be associated
with cancer prognosis; a high expression promotes cell
proliferation, adhesion, migration, and tumorigenesis,
while an inhibited expression delays the development of
CRC tumors [71] . The µ-opioid receptor gene OPRM1 is a
gene that encodes MOR. The genetic polymorphisms of
OPRM1 (A118G) are associated with tumorigenesis. It
has been reported that the G allele of A118G is highly
associated with BC in white people, and people with
G alleles are three times more likely to be diagnosed
with BC. In addition, BC patients with G alleles have
lower specific mortality [74] . Compared with the G/G
genotype, the A/A genotype has significantly higher
risk of esophageal squamous cell carcinoma (ESCC) [75] .
Similar studies have shown that the A allele increases
Figure 2. Mechanism of analgesic effect following MOR activation. the incidence of ESCC in Asians. In addition, evidence
After the opioid binds to the MOR in the presynaptic membrane, it
inhibits voltage-dependent calcium channels, thereby inhibiting the has shown that MOR3 is expressed in a variety of cells,
activation of AMPK receptors and the release of vesicles; after binding such as vascular tissue, and that nitric oxide (NO) is
to the MOR in the postsynaptic membrane, it will decompose Gi into released after morphine action, thus promoting tumor
Gα and Gβγ, in which Gα will inhibit the production of cAMP but angiogenesis [76,77] .
activate the inward rectification of potassium channel Ki3, promoting the
outflow of potassium ions, while Gβγ will flow in with calcium ions at Overall, the bidirectional effect of MOR is evident in
the postsynaptic membrane, which in turn leads to hyperpolarization of tumor development, and many factors, including the
the postsynaptic membrane and inhibits the production of pain. AMPK: number of MOR receptors and drug concentration, lead
AMP-activated protein kinase; cAMP: Cyclic adenosine monophosphate;
Gi: Heterotrimeric inhibitory G protein; Kir3: Inwardly-rectifying to the diametrically opposed effects of the receptor in
[71]
potassium channel; MOR: Mu (µ)-opioid receptor; VGCC: Voltage-gated tumor development . Exploring the mechanism of MOR
calcium channel. Image created with BioRender.com to block its path of promoting tumorigenesis and improve
the prognosis of cancer patients will become a promising
gamma-aminobutyric acid (GABA) neurons, respectively. research direction for the clinical application of opioids
Exogenous opioids (such as morphine) produce analgesic and cancer treatment in the future.
effect by acting on MOR in glutamatergic excitatory
neurons [59,65,66] , while endogenous opioids, which are 3. Relationship between mu-opioid
rapidly released in the spinal cord and supraspinal brain receptor and cancer
regions, inhibit MOR in neurons by acting on GABA to Most cancer patients will inevitably experience cancer
alleviate chronic inflammatory pain [58,67,68] . These studies pain during the disease period. Cancer pain is a type of
indicate that both endogenous and exogenous opioids chronic pain that affects the physical and mental health

Volume 2 Issue 2 (2023) 4 https://doi.org/10.36922/gpd.282