CMTM5 exhibits tumor suppressor activities and is frequently silenced by methylation in carcinoma cell lines.
OBJECTIVE
CMTM5 (CKLF-like MARVEL transmembrane domain containing member 5) is located at 14q11.2, a locus associated with multiple cancers. It has six RNA splicing variants with CMTM5-v1 as the major one. We explored its expression pattern in normal tissues and tumor cell lines, as well as its functions in carcinoma cells.


METHODS
We evaluated CMTM5 expression by semiquantitative reverse transcription-PCR (RT-PCR) in normal tissues and carcinoma cell lines of cervical, breast, nasopharyngeal, lung, hepatocellular, esophageal, gastric, colon, and prostate. We further examined CMTM5 promoter methylation in these cell lines. We also analyzed CMTM5 expression after 5-aza-2'-deoxycytidine treatment and genetic demethylation and the functional consequences of restoring CMTM5 in HeLa and PC-3 cells.


RESULTS
CMTM5-v1 is broadly expressed in human normal adult and fetal tissues, but undetectable or down-regulated in most carcinoma cell lines. Its promoter methylation was detected in virtually all the silenced or down-regulated cell lines. The silencing of CMTM5 could be reversed by pharmacologic demethylation or genetic double-knockout of DNMT1 and DNMT3B, indicating methylation-mediated mechanism. Restoration of CMTM5-v1 suppressed carcinoma cell proliferation, migration, and invasion.


CONCLUSIONS
These results indicate that CMTM5 exhibits tumor suppressor activities, but with frequent epigenetic inactivation in carcinoma cell lines.
Shao
Luning
L
Peking University Center for Human Disease Genomics, 38 [corrected] Xueynun Road, Beijing, 100083, China.
Cui
Yan
Y
Li
Hongyu
H
Liu
Yanan
Y
Zhao
Hongshan
H
Wang
Yu
Y
Zhang
Yingmei
Y
Ng
Ka Man
KM
Han
Wenling
W
Ma
Dalong
D
Tao
Qian
Q
D001483:Base Sequence; D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism*; D045744:Cell Line, Tumor; D018925:Chemokines / Q000096:biosynthesis* / Q000235:genetics* / Q000502:physiology; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006367:HeLa Cells; D006801:Humans; D062792:MARVEL Domain-Containing Proteins; D008297:Male; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism*; D014018:Tissue Distribution; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000502:physiology
C525020:CMTM5 protein, human; D018925:Chemokines; D062792:MARVEL Domain-Containing Proteins; D025521:Tumor Suppressor Proteins