INT120164

Context Info Confidence 0.77 First Reported 2004 Last Reported 2008 Negated 3 Speculated 0 Reported most in Body Documents 47 Total Number 47 Disease Relevance 36.89 Pain Relevance 0.94

cell adhesion (OPCML) plasma membrane (OPCML)

Anatomy Link Frequency brain 3 nervous system 3 T29H 2 lung 2 SW480 1 OPCML (Homo sapiens)

Pain Link Frequency Relevance Heat Opioid 88 100.00 metalloproteinase 6 24.40 imagery 2 5.00 antagonist 2 5.00 chemokine 1 5.00 agonist 1 5.00 medulla 1 5.00 Catecholamine 1 5.00

Disease Link Frequency Relevance Heat Adhesions 354 100.00 Nasopharynx Cancer 874 99.88 Cancer 2428 99.84 Carcinoma 494 99.84 Adenocarcinoma 167 99.32 Esophageal Cancer 116 99.02 Stress 685 98.88 Ovarian Cancer 171 98.84 Lymphatic System Cancer 572 97.64 Shock 77 95.16

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Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

One of the in silico identified genes is OPCML (opioid binding protein/cell adhesion molecule-like gene), also known as OBCAM (opioid binding cell adhesion molecule), belonging to the IgLON (OPCML, LSAMP, NEGR1 and HNT) family of glycosylphosphatidylinositol (GPI)-anchored cell adhesion molecules that are highly expressed in the nervous system [15]–[18] and involved in cell adhesion and cell-cell recognition [19].

Gene_expression (expressed) of IgLON in nervous system associated with opioid and adhesions

1) Confidence 0.77 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2500176 Disease Relevance 1.57 Pain Relevance 0.20

Interestingly, OPCML-v2 could not be activated in any drug treated cell line or DKO cell line (Fig. 4A, 4B), suggesting that the expression of OPCML-v2, being tissue-specific, is controlled by other intrinsic mechanism(s), and that its silencing in multiple carcinoma cell lines is controlled by methylation-independent mechanism or, less likely, that its upregulation level is below the limit of detection.

Gene_expression (expression) of OPCML-v2 associated with carcinoma

2) Confidence 0.77 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2500176 Disease Relevance 0.62 Pain Relevance 0

One of the in silico identified genes is OPCML (opioid binding protein/cell adhesion molecule-like gene), also known as OBCAM (opioid binding cell adhesion molecule), belonging to the IgLON (OPCML, LSAMP, NEGR1 and HNT) family of glycosylphosphatidylinositol (GPI)-anchored cell adhesion molecules that are highly expressed in the nervous system [15]–[18] and involved in cell adhesion and cell-cell recognition [19].

Gene_expression (expressed) of OPCML in nervous system associated with opioid and adhesions

3) Confidence 0.77 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2500176 Disease Relevance 1.56 Pain Relevance 0.20

We found that the expression of OPCML-v1 was dramatically elevated in cell lines with an unmethylated promoter, after exposure to various stresses, such as heat shock, UV irradiation and H2O2 treatment.

Gene_expression (expression) of OPCML-v1 associated with stress and shock

4) Confidence 0.77 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2500176 Disease Relevance 1.20 Pain Relevance 0

Furthermore, although singly transfected cell lines have little effect on neurite outgrowth, CHO cell lines expressing both CEPU-1 and OBCAM (Diglon-CO) inhibit neurite outgrowth from cerebellar granule cells.

Gene_expression (expressing) of OBCAM in neurite

5) Confidence 0.70 Published 2004 Journal J. Cell. Sci. Section Abstract Doc Link 15265982 Disease Relevance 0.36 Pain Relevance 0.07

p53 could induce OPCML expression in the H1299 cell line with a partially methylated promoter, in a dosage-dependent manner (Fig. 7C).

Gene_expression (expression) of OPCML

6) Confidence 0.68 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2500176 Disease Relevance 1.21 Pain Relevance 0

Notably, expression of OPCML-v2 remained undetectable in virtually all cell lines evaluated, including normal cell lines.

Gene_expression (expression) of OPCML-v2

7) Confidence 0.68 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2500176 Disease Relevance 0.63 Pain Relevance 0

Using primers specific to the common exons of OPCML transcripts, we found the expression of OPCML in several tumor cell lines (Hep3B, H292, SW480, L1236), where the OPCML-v1 and v2 were totally silenced (Fig. 1F), indicating transcription of OPCML from alternative unknown promoters.

Gene_expression (expression) of OPCML in SW480 associated with cancer

8) Confidence 0.68 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2500176 Disease Relevance 0.15 Pain Relevance 0

The treatment resulted in the restoration of OPCML-v1 expression in all tumor cell lines (Fig. 4A).

Gene_expression (expression) of OPCML-v1 associated with cancer

9) Confidence 0.68 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2500176 Disease Relevance 0.62 Pain Relevance 0

Ecotopic expression of OPCML led to significant inhibition of both anchorage-dependent and -independent growth of carcinoma cells with endogenous silencing.

Gene_expression (expression) of OPCML associated with carcinoma

10) Confidence 0.68 Published 2008 Journal PLoS ONE Section Abstract Doc Link PMC2500176 Disease Relevance 1.36 Pain Relevance 0

Pharmacologic and genetic demethylation restored OPCML-v1 expression

Gene_expression (expression) of OPCML-v1

11) Confidence 0.68 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2500176 Disease Relevance 0.75 Pain Relevance 0

Whereas OPCML-v1 was widely expressed in normal adult tissues, OPCML-v2 showed a more tissue-specific expression profile, being highly expressed in few tissues including brain.

Gene_expression (expressed) of OPCML-v1 in brain

12) Confidence 0.68 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2500176 Disease Relevance 0.35 Pain Relevance 0

In contrast to its expression in adult tissues, OPCML-v2 was expressed at moderate to high levels in all fetal tissues except for placenta.

Neg (except) Gene_expression (expressed) of OPCML-v2 in placenta

13) Confidence 0.68 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2500176 Disease Relevance 0.28 Pain Relevance 0

In summary, we found that the expression of OPCML-v1 (NM_002545), a major transcript of this TSG, is frequently silenced or down-regulated in multiple tumors.

Gene_expression (expression) of OPCML-v1 associated with cancer

14) Confidence 0.68 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2500176 Disease Relevance 1.08 Pain Relevance 0

In addition, ectopic expression of OPCML in carcinoma cells lacking its expression led to dramatic anchorage-dependent and –independent growth inhibition.

Gene_expression (expression) of OPCML associated with carcinoma

15) Confidence 0.68 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2500176 Disease Relevance 1.09 Pain Relevance 0

OPCML-v1 was widely expressed in all normal adult and fetal tissues except for placenta and peripheral blood mononuclear cells (PBMC), though at varying levels (highly expressed in brain, kidney, spleen, stomach, trachea, testis, cervix, ovary and prostate, and weakly in lung, breast, and bone marrow) (Fig. 1E).

Neg (except) Gene_expression (expressed) of OPCML-v1 in bone marrow

16) Confidence 0.68 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2500176 Disease Relevance 0 Pain Relevance 0

It was found that OPCML-v1 expression was dramatically reduced or completely silenced in multiple carcinoma cell lines of nasopharynx, esophagus, breast, cervix, stomach, lung, colon, liver and prostate, as well as in virtually all lymphoma cell lines examined (Fig. 2C and Figure S1), but readily detected in glioma cell lines (Fig. 2D).

Gene_expression (expression) of OPCML-v1 in stomach associated with lymphatic system cancer, carcinoma and glioma

17) Confidence 0.68 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2500176 Disease Relevance 0.64 Pain Relevance 0

Previously, OPCML was shown to be strongly expressed in brain and normal ovarian epithelia [20].

Gene_expression (expressed) of OPCML in brain

18) Confidence 0.68 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2500176 Disease Relevance 0 Pain Relevance 0

Pharmacological and genetic demethylation restored OPCML expression, indicating a direct epigenetic silencing.

Gene_expression (expression) of OPCML

19) Confidence 0.68 Published 2008 Journal PLoS ONE Section Abstract Doc Link PMC2500176 Disease Relevance 1.44 Pain Relevance 0

Among the IgLON family, OPCML was the first member reported to possess tumor suppressor functions in epithelial ovarian cancer, being frequently silenced genetically and epigenetically at the early step of ovarian carcinogenesis [20].

Gene_expression (family) of OPCML associated with cancer and ovarian cancer

20) Confidence 0.67 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2500176 Disease Relevance 0.97 Pain Relevance 0

General Comments

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