Decreased expression of Kallmann syndrome 1 sequence gene (KAL1) contributes to oral squamous cell carcinoma progression and significantly correlates with poorly differentiated grade.

Abstract

BACKGROUND:

Kallmann syndrome 1 sequence gene (KAL1) protein is an extracellular matrix associated protein which plays vital roles in neurons development and cell migration. However, its biological functions and clinical implications have yet not been revealed in oral carcinogenesis. The objective of the study was to evaluate the role of KAL1 in oral cancer and determine clinical significance of KAL1 in oral squamous cell carcinomas (OSCCs).

METHODS:

The expression pattern of KAL1 was examined in a testing cohort including OSCCs (n = 42) and paired adjacent tissues (PATs) (n = 14) by real-time PCR. The result was further validated in a validating cohort of OSCCs (n = 32). Correlation between clinicopathological parameters and KAL1 mRNA levels was analyzed by Kruskal-Wallis test. In vitro, the effects of KAL1 ablation through siRNA-mediated knockdown on the proliferation of OSCC cells were determined by CCK-8, BrdU, and colonies formation assays, respectively. In addition, cell cycle distribution was further evaluated by cytometry.

RESULTS:

We observed that remarkably decreased expression of KAL1 mRNA in two independent cohorts (P = 0.0002 and P = 0.033, respectively). Furthermore, downregulated KAL1 mRNA was significantly associated with worse pathological grade (P = 0.013 and P = 0.035, respectively). Upon KAL1 silencing, the proliferation and colonies formation potentials of OSCC cells were notably promoted by accelerating G1 to M phase transition.

CONCLUSION:

These data indicated that KAL1 plays a potential suppressive role on OSCC initiation and progression, and KAL1 gene may serve as an adjuvant biomarker for the identification of pathological grade.

• Authors: Jiannan Liu, Wei Cao, Wantao Chen, Liqun Xu, Chenping Zhang
• Journal: Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology (J Oral Pathol Med) Vol. 44 Issue 2 Pg. 109-14 (Feb 2015) ISSN: 1600-0714 [Electronic] Denmark
• PMID: 25060050 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Chemical References

• ANOS1 protein, human
• Extracellular Matrix Proteins
• Nerve Tissue Proteins
• RNA, Small Interfering
• Tumor Suppressor Proteins
• Bromodeoxyuridine
• Sincalide

Topics

• Bromodeoxyuridine
• Carcinogenesis (chemistry, pathology)
• Carcinoma, Squamous Cell (chemistry, pathology)
• Cell Culture Techniques
• Cell Cycle Checkpoints
• Cell Differentiation
• Cell Division
• Cell Line, Tumor
• Cell Proliferation
• Cohort Studies
• Disease Progression
• Extracellular Matrix Proteins (analysis, genetics)
• Female
• G1 Phase
• Gene Expression Regulation, Neoplastic (genetics)
• Gene Knockdown Techniques
• Gene Silencing
• Humans
• Male
• Middle Aged
• Mouth Mucosa (chemistry, pathology)
• Mouth Neoplasms (chemistry, pathology)
• Neoplasm Grading
• Nerve Tissue Proteins (analysis, genetics)
• RNA, Small Interfering (genetics)
• Sincalide
• Tumor Suppressor Proteins (analysis)