Histone variant H3F3A promotes lung cancer cell migration through intronic regulation.
Although several somatic single nucleotide variations in histone H3.3 have been investigated as cancer drivers, other types of aberration have not been well studied. Here, we demonstrate that overexpression of H3F3A, encoding H3.3, is associated with lung cancer progression and promotes lung cancer cell migration by activating metastasis-related genes. H3.3 globally activates gene expression through the occupation of intronic regions in lung cancer cells. Moreover, H3.3 binding regions show characteristics of regulatory DNA elements. We show that H3.3 is deposited at a specific intronic region of GPR87, where it modifies the chromatin status and directly activates GPR87 transcription. The expression levels of H3F3A and GPR87, either alone or in combination, are robust prognostic markers for early-stage lung cancer, and may indicate potential for the development of treatments involving GPR87 antagonists. In summary, our results demonstrate that intronic regulation by H3F3A may be a target for the development of novel therapeutic strategies.
Specific Organs Cancer Branch, Research Institute, National Cancer Center, Goyang, Gyeonggi 10408, Republic of Korea.
Seong-Min
SM
Park
Specific Organs Cancer Branch, Research Institute, National Cancer Center, Goyang, Gyeonggi 10408, Republic of Korea.
Eun-Young
EY
Choi
Department of Bio and Brain Engineering, KAIST, Daejeon 34141, Republic of Korea.
Mingyun
M
Bae
Precision Medicine Branch, Research Institute, National Cancer Center, Goyang, Gyeonggi 10408, Republic of Korea.
Sunshin
S
Kim
Specific Organs Cancer Branch, Research Institute, National Cancer Center, Goyang, Gyeonggi 10408, Republic of Korea.|Department of System Cancer Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Gyeonggi 10408, Republic of Korea.
Jong Bae
JB
Park
Specific Organs Cancer Branch, Research Institute, National Cancer Center, Goyang, Gyeonggi 10408, Republic of Korea.
Heon
H
Yoo
Department of Bio and Brain Engineering, KAIST, Daejeon 34141, Republic of Korea.
Jung Kyoon
JK
Choi
Specific Organs Cancer Branch, Research Institute, National Cancer Center, Goyang, Gyeonggi 10408, Republic of Korea.
Youn-Jae
YJ
Kim
Specific Organs Cancer Branch, Research Institute, National Cancer Center, Goyang, Gyeonggi 10408, Republic of Korea.
Seung-Hoon
SH
Lee
Department of System Cancer Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Gyeonggi 10408, Republic of Korea.
In-Hoo
IH
Kim
D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D002843:Chromatin / Q000737:chemistry; D018450:Disease Progression; D018628:Gene Dosage; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006657:Histones / Q000378:metabolism*; D006801:Humans; D007438:Introns; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D009154:Mutation; D009362:Neoplasm Metastasis; D011379:Prognosis; D016016:Proportional Hazards Models; D049368:Receptors, Lysophosphatidic Acid / Q000378:metabolism; D050436:Regulatory Elements, Transcriptional
D002843:Chromatin; C526276:GPR87 protein, human; D006657:Histones; D049368:Receptors, Lysophosphatidic Acid
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