Clinical significance of high mobility group A2 in human gastric cancer and its relationship to let-7 microRNA family.
OBJECTIVE
The high mobility group A2 (HMGA2) nonhistone chromosomal protein can modulate transcription by altering chromatin architecture. HMGA2 is highly expressed during embryogenesis and in various benign and malignant tumors. Recent studies report that HMGA2 is negatively regulated by the let-7 microRNA (miRNA) family. However, no studies have examined the clinical significance of HMGA2 and its relationship to the let-7 miRNA family in gastric cancer.


METHODS
Using quantitative real-time reverse transcription-PCR, we analyzed HMGA2 expression with respect to various clinicopathologic factors in 110 patients with gastric cancer. We also did an association study comparing HMGA2 expression and let-7 miRNA family expression in gastric cancer.


RESULTS
Expression of HMGA2 in cancerous tissues was significantly higher than in noncancerous tissues (P < 0.05). Elevated HMGA2 expression was significantly correlated with serosal invasion (P < 0.05) and poor clinical prognosis (P < 0.05). A multivariate analysis showed that HMGA2 expression status was an independent prognostic factor (P < 0.05). An inverse correlation between HMGA2 and let-7a was found in gastric cancer cell lines (P = 0.08). The expressions of let-7a, let-7b, and let-7c in gastric cancer patients with low HMGA2 expression were significantly higher than those with high HMGA2 expression (P < 0.05).


CONCLUSIONS
High expression of HMGA2 in gastric cancer correlates with tumor invasiveness and is an independent prognostic factor. Furthermore, our findings suggest that HMGA2 is negatively regulated by the let-7 miRNA family in human gastric cancer.
Motoyama
Kazuo
K
Department of Molecular and Surgical Oncology, Medical Institute of Bioregulation, Kyushu University, Beppu, Japan.
Inoue
Hiroshi
H
Nakamura
Yoshito
Y
Uetake
Hiroyuki
H
Sugihara
Kenichi
K
Mori
Masaki
M
D005260:Female; D025743:HMGA2 Protein / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D035683:MicroRNAs / Q000502:physiology*; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis; D013274:Stomach Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology
D025743:HMGA2 Protein; D035683:MicroRNAs; D012333:RNA, Messenger; C487931:mirnlet7 microRNA, human