Expression analysis and biological regulation of silencing regulatory protein 6 (SIRT6) in cutaneous squamous cell carcinoma<sup/>

Chen, Sai; Chen, Hongxia; Wang, Xu; Zhang, Dongmei; Zhang, Li; Cheng, Jiawei; Zhang, Qi; Hua, Zhixiang; Miao, Xu; Shi, Jian

doi:10.1016/j.abd.2023.08.010

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Sumário

Original Article • An. Bras. Dermatol. 99 (4) • 2024 • https://doi.org/10.1016/j.abd.2023.08.010 copy

Expression analysis and biological regulation of silencing regulatory protein 6 (SIRT6) in cutaneous squamous cell carcinoma^☆ ☆ Study conducted at the Nantong First People’s Hospital, Nantong, China.

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

Background

Cutaneous squamous cell carcinoma (CSCC) is one of the most common types of skin cancer worldwide. Therefore, the identification of biomarkers associated with CSCC progression could aid in the early detection of high-risk squamous cell carcinoma and the development of novel therapeutic strategies.

Objective

This study aimed to investigate the expression patterns of silent mating type Information Regulation 2 homolog 6 (SIRT6) in CSCC and its clinical significance.

Methods

The protein expression level of SIRT6 in tissues was detected by immunohistochemistry, and the correlation between SIRT6 expression and clinicopathological parameters in CSCC patients was analyzed. The relative expression of SIRT6 in CSCC cell lineage and tissue specimens was determined by western blotting and PCR. The effect of SIRT6 silencing on cell proliferation was evaluated using cell counting kit 8. Wound healing, transwell method, and flow cytometry were used to investigate the migration, invasion, and cell cycle distribution/apoptosis of CSCC cells after SIRT6 silencing, respectively. Western blot was used to detect the expression of EMT (Epithelial-Mesenchymal Transition), cycle, apoptosis, and other related proteins.

Results

The high expression of SIRT6 was correlated with the location of cancer tissue and Broder staging in CSCC patients. Knockdown of SIRT6 inhibited the proliferation, migration, invasion and EMT of CSCC cells, and promoted their apoptosis, with cells blocked in G1 phase.

Study limitations

No animal experiments were conducted to further verify the results.

Conclusion

Decreased expression of SIRT6 can inhibit the occurrence and development of CSCC.

Keywords
Biomarkers; Carcinoma, squamous cell; Histology; Sirtuin-6

Evaluation indication	Grading		Score
Positive cell count	0%～25%		1
	26%～50%		2
	51%～75%		3
	76%～100%		4
Staining intensity	No coloring		0
	Faint yellow		1
	Claybank		2
	Tan		3
Expression intensity (Positive cell count × Dyeing strength)	Low expression	Negative (−)	0～3
	Low expression	Weak Positive (+)	4～6
	High expression	Positive (++)	7～9
	High expression	Strong Positive (+++)	10～12

Gene	Primer sequence
SIRT6	F:5′- TGGCAGTCTTCCAGTGTGGTGT-3′
SIRT6	R:5′- CGCTCTCAAAGGTGGTGTCGAA-3′
U6	F:5′- CTCGCTTCGGCAGCACA -3′
U6	R: 5′- AACGCTTCACGAATTTGCGT-3′

Group	Expression of SIRT6		Total	High expression rate
	Low expression (-～+)	High expression (++～+++)
NT	20	0	20	0
AK	26	34	60	56.67%
BD	2	23	25	92.00%
CSCC	6	64	70	91.43%

Clinical features		Number of cases	Low expression (-～+)	High expression (++～+++)	P-value
Gender	Male	26	2	24	0.433
Gender	Female	44	4	40	0.433
Age	≤70	13	1	12	0.207
Age	>70	57	3	52	0.207
Position	Exposure	59	1	58	0.032*
Position	Non-exposure	11	3	8	0.032*
Course of disease	<2-years	39	3	36	0.405
Course of disease	≥2-years	31	1	30	0.405
Invasion depth	≤3-mm	52	2	50	0.128
Invasion depth	>3-mm	18	2	16	0.128
Diameter	≤2-cm	49	3	46	0.316
Diameter	>2-cm	21	1	20	0.316
Broders classification	Ⅰ‒Ⅱ	38	4	34	0.012*
Broders classification	Ⅲ‒Ⅳ	32	0	32	0.012*

Sociedade Brasileira de Dermatologia Av. Rio Branco, 39 18. and., 20090-003 Rio de Janeiro RJ, Tel./Fax: +55 21 2253-6747 - Rio de Janeiro - RJ - Brazil
E-mail: revista@sbd.org.br

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[1] * Corresponding author. E-mail:jsntmcsj@163.com (J. Shi)

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Expression analysis and biological regulation of silencing regulatory protein 6 (SIRT6) in cutaneous squamous cell carcinoma☆ ☆ Study conducted at the Nantong First People’s Hospital, Nantong, China.

Abstract

Background

Objective

Methods

Results

Study limitations

Conclusion

Expression analysis and biological regulation of silencing regulatory protein 6 (SIRT6) in cutaneous squamous cell carcinoma^☆ ☆ Study conducted at the Nantong First People’s Hospital, Nantong, China.