Knockdown of Tubulin Polymerization Promoting Protein Family Member 3 Suppresses Proliferation and Induces Apoptosis in Non-Small-Cell Lung Cancer

Background/Aims: Cervical cancer, which is one of the most aggressive cancers affecting females, has high rates of recurrence and mortality. Small nucleolar RNA host gene 12 (SNHG12) is known to promote the progression of several cancers; however, its exact effects and molecular mechanisms in cervical cancer remain unknown. Methods: Real-time quantitative PCR was used to determine the expression level of SNHG12 in cervical cancer tissues and cell lines. Loss-of-function assays were performed to examine the effect of SNHG12 on the proliferation, apoptosis, migration and invasion of cervical cancer cells in vitro and tumor growth in vivo. Luciferase experiments were employed to explore the interactions between SNHG12 and miR-424-5p. Results: SNHG12 was found to be abnormally elevated in human cervical cancer tissues compared with paired adjacent normal tissues. Moreover, high SNHG12 expression in tumor tissues was significantly correlated with vascular involvement, lymph node metastasis, advanced FIGO stage and poor prognosis. Furthermore, the knockdown of SNHG12 was found to inhibit proliferation, migration and invasion of cervical cancer cells in vitro, and silencing SNHG12 was shown to suppress tumor growth in a nude mouse model. Mechanistic studies showed that SNHG12 functioned as an endogenous sponge for miR-424-5p, thereby downregulating the expression of miR-424-5p in cervical cancer. Furthermore, the inhibition of miR-424-5p in SNHG12-depleted cells partially reversed the effects on cervical cancer cell apoptosis, adhesion and invasion. Conclusion: In summary, our findings suggest that the tumor-promoting role of SNHG12 is to function as a molecular sponge, which negatively regulates miR-424-5p. These findings may provide a potent therapeutic target for cervical cancer.

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“…IHC staining was performed using a Ki-67 (Abcam, CA, USA) antibody according to the previous report [20]. …”

Section: Methodsmentioning

confidence: 99%

Upregulation of Long Non-Coding RNA Small Nucleolar RNA Host Gene 12 Contributes to Cell Growth and Invasion in Cervical Cancer by Acting as a Sponge for MiR-424-5p

Dong

Wang

et al. 2018

Cell Physiol Biochem

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“…Ki67 is a nuclear protein that is closely linked to the proliferative potential of tumor. Recently, Ki67 was identified as an important prognostic factor for many tumor entities with respect to chemosensitivity and disease recurrence/death (Falato et al 2014;Li et al 2016;Rowe et al 2016). Its prognostic value in ovarian carcinoma remains controversial (Liu et al 2012;Masoumi-Moghaddam et al 2015;Feng et al 2016;Green et al 2016) and its correlation with VASH1 is not well known.…”

Section: Discussionmentioning

confidence: 99%

Vasohibin-1 Is a Poor Prognostic Factor of Ovarian Carcinoma

Sano

Kanomata

Suzuki

et al. 2017

Tohoku J. Exp. Med.

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Vasohibin-1 (VASH1) is an identified negative feedback inhibitor of angiogenesis induced by vascular endothelial growth factor (VEGF) in vascular endothelial cells (ECs). Expression of VASH1 has been reported not only in ECs of normal tissue, but also in ECs surrounding malignant tumors. In malignant tumors, VASH1 is also gaining attention as a prognosis prediction marker. The aim of this study is to investigate the correlation between VASH1 expression and vascular-related factors and various clinicopathological outcomes in clinical cases of ovarian carcinoma. We retrospectively analyzed clinical records of 58 patients with ovarian carcinoma. The expression patterns of VASH1 and other vascularrelated factors (CD31 as markers of microvessel density (MVD), VEGF receptor type 2 (VEGFR2), D2-40 as markers of lymphovessel density), and Ki67 (as proliferation markers of cancer cells) were examined immunohistochemically. We studied the correlation between immunohistochemical expression and overall survival. VASH1 expression pattern significantly differed between Federation of Obstetrics and Gynecology (FIGO) Stages. Numbers of VASH1-positive vessels had a significant positive correlation with MVD (Speaman's correlation coefficient (ρ) was 0.51, p < 0.001), VEGFR2-positive vessels (ρ = 0.61, p < 0.001), and percentage of Ki67 (ρ = 0.28, p = 0.034). The Cox univariable analyses revealed that the group of high VASH1 expression (> 14.6 vessels per mm 2 ) at Stages I-III is a prognostic factor (HR = 3.3, 95%CI = 0.4-8.4; p = 0.013). Our results indicate that VASH1 expression in ovarian carcinoma is significantly associated with vascular-related factors and Ki67 expression. We propose that VASH1 is a prognostic marker in ovarian carcinoma.

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“…Knockdown of TPPP3 expression by RNA interference results in Lewis lung carcinoma (LLC) cell growth inhibition and cell cycle arrest demonstrating a lineage-specific dependency of lung cancer on TPPP3 [11]. Further investigation showed that inhibition of TPPP3 attenuated cell proliferation by inducing cell apoptosis and arresting cell cycle [10]. However, the potential role of TPPP3 in NSCLC development and metastasis remains largely unknown.…”

Section: Introductionmentioning

confidence: 99%

“…We have previously found that TPPP3 was significantly over-expressed in human NSCLC and associated with short overall survival [10]. Knockdown of TPPP3 expression by RNA interference results in Lewis lung carcinoma (LLC) cell growth inhibition and cell cycle arrest demonstrating a lineage-specific dependency of lung cancer on TPPP3 [11].…”

Section: Introductionmentioning

confidence: 99%

“…In addition, silencing of Twist1 sensitized NSCLC cells to cisplatin via stimulating AMPK-induced mTOR/S6K1 inhibition which led to a decrease of Mcl-1 protein [18]. Our previous study showed that TPPP3 modulates the cell growth by activating phosphorylation of STAT3 [10]. It was previously shown that STAT3 directly binds to the promoter of Twist1 and activated its transcriptional activity in human cancer cells [19,20].…”

Section: Introductionmentioning

confidence: 99%

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TPPP3 Promotes Cell Proliferation, Invasion and Tumor Metastasis via STAT3/ Twist1 Pathway in Non-Small-Cell Lung Carcinoma

Li¹,

Bai²,

Xu³

et al. 2018

Cell Physiol Biochem

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Background/Aims: Non-small-cell lung carcinoma (NSCLC) is the leading cause of cancer death, with tumor metastasis being mainly responsible for lung cancer-associated mortality. Our previous studies have found that tubulin polymerization promoting protein family member 3 (TPPP3) acted as a potential oncogene in NSCLC. Little is known about the function of TPPP3 in tumor metastasis. Methods: RT-qPCR and IHC were used to investigate the expression of TPPP3 in NSCLC tissues. CCK8 assay and transwell assay were used to measure proliferation and migration of NSCLC cells in vitro and xenograft model was performed to assess the tumor growth and metastasis in vivo. Results: In the present study, upregulation of TPPP3 was found to correlate with an increased metastasis capability of NSCLC. Ectopic expression of TPPP3 significantly enhanced cell proliferation in vitro and promoted tumor growth in vivo. Furthermore, overexpression of TPPP3 remarkably promoted NSCLC cell migration and invasion along with the upregulation of Twist1 both in vitro and in vivo. Further investigations showed that activation of STAT3 was required for TPPP3-mediated upregulation of Twist1, cell migration and invasion. A strong positive correlation between TPPP3 and Twist1 expression was identified in NSCLC tissues. Patients with low TPPP3 or low Twist1 in NSCLC tissues had a better prognosis with longer overall survival (OS) and disease-free survival (DFS). Conclusion: Overall, this study demonstrates that TPPP3 promotes the metastasis of NSCLC through the STAT3/Twist1 pathway.

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Knockdown of Tubulin Polymerization Promoting Protein Family Member 3 Suppresses Proliferation and Induces Apoptosis in Non-Small-Cell Lung Cancer

Cited by 22 publications

References 26 publications

Upregulation of Long Non-Coding RNA Small Nucleolar RNA Host Gene 12 Contributes to Cell Growth and Invasion in Cervical Cancer by Acting as a Sponge for MiR-424-5p

Upregulation of Long Non-Coding RNA Small Nucleolar RNA Host Gene 12 Contributes to Cell Growth and Invasion in Cervical Cancer by Acting as a Sponge for MiR-424-5p

Vasohibin-1 Is a Poor Prognostic Factor of Ovarian Carcinoma

TPPP3 Promotes Cell Proliferation, Invasion and Tumor Metastasis via STAT3/ Twist1 Pathway in Non-Small-Cell Lung Carcinoma

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