Elevated FAM134B expression induces radiation-sensitive in hepatocellular carcinoma
Abstract Background Previous studies have shown that Family with sequence similarity 134 member B (FAM134B) was involved in the occurrence and development of malignancy, however, the function and molecular mechanism of FAM134B in Hepatocellular Carcinoma (HCC) radiotherapy resistance remain unclear....
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-07-01
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| Series: | BMC Cancer |
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| Online Access: | https://doi.org/10.1186/s12885-023-11030-x |
| _version_ | 1797774132719386624 |
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| author | Binhui Xie Yuankang Xie Cuifu Fang Baiyin Zhong Rong Ye Jianhong Zhang Qingquan Liu Heping Li |
| author_facet | Binhui Xie Yuankang Xie Cuifu Fang Baiyin Zhong Rong Ye Jianhong Zhang Qingquan Liu Heping Li |
| author_sort | Binhui Xie |
| collection | DOAJ |
| description | Abstract Background Previous studies have shown that Family with sequence similarity 134 member B (FAM134B) was involved in the occurrence and development of malignancy, however, the function and molecular mechanism of FAM134B in Hepatocellular Carcinoma (HCC) radiotherapy resistance remain unclear. Therefore, it may clinical effective to clarify the molecular mechanism and identify novel biomarker to overcome radiotherapy resistance in HCC. Methods The protein and mRNA expression of FAM134B were determined using Real-time PCR and Western blot, respectively. IHC assay was performed to investigate the association between FAM134B expression and the clinicopathological characteristics of 132 HCC patients. Functional assays, such as in situ model, colon formation, FACS, and Tunel assay were used to determine the oncogenic role of FAM134B in human HCC progression. Furthermore, western blotting and luciferase assay were used to determine the mechanism of FAM134B promotes radiation-sensitive in HCC cells. Results We noted that FAM134B was downregulated in HCC, which was correlated with the radiation resistance in patients with HCC. Overexpression of FAM134B contribute to radiation sensitive in HCC; however, inhibition of FAM134B confers HCC cell lines to radiation resistance both in vitro and in vivo. Moreover, we found that FAM134B interacts with FMS related receptor tyrosine kinase 3 (FLT3) and downregulation of FAM134B activated JAK/Stat3 signaling pathway. Importantly, pharmacological inhibition of JAK/Stat3 signaling pathway significantly counteracted downregulation of FAM134B-induced radiation resistance and enhanced radiation therapeutic efficacy in HCC. Conclusions Our findings suggest that FAM134B may be a potential therapeutic biomarker for the treatment of HCC patients with radiotherapy tolerance. |
| first_indexed | 2024-03-12T22:16:32Z |
| format | Article |
| id | doaj.art-1b54f97365cf4367aa0f71deec20798c |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-03-12T22:16:32Z |
| publishDate | 2023-07-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-1b54f97365cf4367aa0f71deec20798c2023-07-23T11:17:11ZengBMCBMC Cancer1471-24072023-07-0123111110.1186/s12885-023-11030-xElevated FAM134B expression induces radiation-sensitive in hepatocellular carcinomaBinhui Xie0Yuankang Xie1Cuifu Fang2Baiyin Zhong3Rong Ye4Jianhong Zhang5Qingquan Liu6Heping Li7Department of Hepatobiliary Surgery, the First Affiliated Hospital of Gannan Medical UniversityDepartment of Hepatobiliary Surgery, the First Affiliated Hospital of Gannan Medical UniversityDepartment of general surgery III, the First Affiliated Hospital of Gannan Medical UniversityDepartment of Hepatobiliary Surgery, the First Affiliated Hospital of Gannan Medical UniversityDepartment of general surgery III, the First Affiliated Hospital of Gannan Medical UniversityDepartment of Hepatobiliary Surgery, the First Affiliated Hospital of Gannan Medical UniversityDepartment of Hepatobiliary Surgery, the First Affiliated Hospital of Gannan Medical UniversityDepartment of Medical Oncology, the First Affiliated Hospital of Sun Yat-sen UniversityAbstract Background Previous studies have shown that Family with sequence similarity 134 member B (FAM134B) was involved in the occurrence and development of malignancy, however, the function and molecular mechanism of FAM134B in Hepatocellular Carcinoma (HCC) radiotherapy resistance remain unclear. Therefore, it may clinical effective to clarify the molecular mechanism and identify novel biomarker to overcome radiotherapy resistance in HCC. Methods The protein and mRNA expression of FAM134B were determined using Real-time PCR and Western blot, respectively. IHC assay was performed to investigate the association between FAM134B expression and the clinicopathological characteristics of 132 HCC patients. Functional assays, such as in situ model, colon formation, FACS, and Tunel assay were used to determine the oncogenic role of FAM134B in human HCC progression. Furthermore, western blotting and luciferase assay were used to determine the mechanism of FAM134B promotes radiation-sensitive in HCC cells. Results We noted that FAM134B was downregulated in HCC, which was correlated with the radiation resistance in patients with HCC. Overexpression of FAM134B contribute to radiation sensitive in HCC; however, inhibition of FAM134B confers HCC cell lines to radiation resistance both in vitro and in vivo. Moreover, we found that FAM134B interacts with FMS related receptor tyrosine kinase 3 (FLT3) and downregulation of FAM134B activated JAK/Stat3 signaling pathway. Importantly, pharmacological inhibition of JAK/Stat3 signaling pathway significantly counteracted downregulation of FAM134B-induced radiation resistance and enhanced radiation therapeutic efficacy in HCC. Conclusions Our findings suggest that FAM134B may be a potential therapeutic biomarker for the treatment of HCC patients with radiotherapy tolerance.https://doi.org/10.1186/s12885-023-11030-xFAM134BFLT3HCCJAK/Stat3 signaling pathwayRadiotherapy-resistance |
| spellingShingle | Binhui Xie Yuankang Xie Cuifu Fang Baiyin Zhong Rong Ye Jianhong Zhang Qingquan Liu Heping Li Elevated FAM134B expression induces radiation-sensitive in hepatocellular carcinoma BMC Cancer FAM134B FLT3 HCC JAK/Stat3 signaling pathway Radiotherapy-resistance |
| title | Elevated FAM134B expression induces radiation-sensitive in hepatocellular carcinoma |
| title_full | Elevated FAM134B expression induces radiation-sensitive in hepatocellular carcinoma |
| title_fullStr | Elevated FAM134B expression induces radiation-sensitive in hepatocellular carcinoma |
| title_full_unstemmed | Elevated FAM134B expression induces radiation-sensitive in hepatocellular carcinoma |
| title_short | Elevated FAM134B expression induces radiation-sensitive in hepatocellular carcinoma |
| title_sort | elevated fam134b expression induces radiation sensitive in hepatocellular carcinoma |
| topic | FAM134B FLT3 HCC JAK/Stat3 signaling pathway Radiotherapy-resistance |
| url | https://doi.org/10.1186/s12885-023-11030-x |
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