Page 5 - D. Cancer biology

Regulatory mechanism of MKK7 by METTL21B in gastric cancer

Long You , Yo Han Hong , Jae Gwang Park , Nur Aziz , Chaoran Song , Wooram Choi , Jieun Oh , Han Gyung Kim , and Jae Youl Cho 1
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1 Integrative biotechnology, Sungkyunkwan University, Suwon 16419, Korea
2 Colorectal Cancer Branch, National Cancer Center, Goyang 10408, Korea
BACKGROUND AIM
Gastric cancer is difficult to diagnose early because there To figure out clinical relevance and biological
are no symptoms at the beginning of development, and significance of METTL21B in human gastric cancer.
most of the advanced cancer is diagnosed as advanced
cancer, and treatment methods are very limited and poor. METHODS
Mitogen-activated protein kinase pathway is a major cell-
mediated cascade that regulates processes that regulate Clinical impact of METTL21B was assessed in total
tumorigenic responses. These responses are regulated by 426 patients with gastric cancer. Immunoblot and
post-translational modifications (PTMs). Methylation as realtime PCR were used to detect METTL21B
one of PTMs affects various physiological processes such expression in cell lines and patient samples.
as cell differentiation, proteolysis, signaling, regulatory QunatSeq 3’ mRNA-Seq was used to screen the
processes, and gene expression regulation. METTL21B is target genes of METTL21B. Biological functions of
a non-histone protein lysine methyltransferase. The METTL21B were examined in vitro and in vivo.
recently discovered METTL21B has reported little of its Immunoprecipitation and mass spectrometry were
function and methylated substrates. conducted to identify the specific binding partners and
methylation sites

RESULTS

Fig 1. METTL21B related to gastric tumorigenesis Figure 1 Figure 2
and cancer progression.
Using gastric cancer patient samples from Asia
Cancer Research Group (ACRG) database and Ajou
University Hospital, METTL21B suppression
correlated with gastric cancer and was independently
associated with poor survival and recurrence.
METTL21B expression was suppressed in human
gastric cancer specimens and cell lines.
Fig 2. METTL21B regulated MKK7 mediated AP-1
signaling pathway by methylation dependent
manner.
MKK7 is a novel binding partner of METTL21B.
METTL21B interacted with MKK7 and methylated at Figure 3
lysine 296. And then, we also verified that
METTL21B mediated methylation of MKK7 at K296
is important to regulate MAPK signaling pathway.
Fig 3. METTL21B involved in colony forming
ability and motility of gastric cancer.
METTL21B decreased cell motility, invasion and
colony forming ability of gastric cancer cells on over-
expression condition. Knock-down METTL21B leads
to higher level of metastasis than control in vitro.
Also, the depletion of METTL21B will increase the
numbers of tumor nodules in vivo.
CONCLUSION REFERENCES ACKNOWLEDGEMENTS

[1] Van Cutsem, Eric, et al. Gastric cancer. The Lancet 388, 2654-2664 This research was supported by the Basic Science
In conclusion, we suggest that (2016). Research Program through the National Research
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