The GATAD2B-NuRD complex drives DNA:RNA hybrid-dependent chromatin boundary formation upon DNA damage.

Double-strand breaks (DSBs) are the most lethal form of DNA damage. Transcriptional activity at DSBs, as well as transcriptional repression around DSBs, are both required for efficient DNA repair. The chromatin landscape defines and coordinates these two opposing events. However, how the open and condensed chromatin architecture is regulated remains unclear. Here, we show that the GATAD2B-NuRD complex associates with DSBs in a transcription- and DNA:RNA hybrid-dependent manner, to promote histone deacetylation and chromatin condensation. This activity establishes a spatio-temporal boundary between open and closed chromatin, which is necessary for the correct termination of DNA end resection. The lack of the GATAD2B-NuRD complex leads to chromatin hyperrelaxation and extended DNA end resection, resulting in homologous recombination (HR) repair failure. Our results suggest that the GATAD2B-NuRD complex is a key coordinator of the dynamic interplay between transcription and the chromatin landscape, underscoring its biological significance in the RNA-dependent DNA damage response.

VCP/p97 UFMylation stabilizes BECN1 and facilitates the initiation of autophagy.

Macroautophagy/autophagy is essential for the degradation and recycling of cytoplasmic materials. The initiation of this process is determined by phosphatidylinositol-3-kinase (PtdIns3K) complex, which is regulated by factor BECN1 (beclin 1). UFMylation is a novel ubiquitin-like modification that has been demonstrated to modulate several cellular activities. However, the role of UFMylation in regulating autophagy has not been fully elucidated. Here, we found that VCP/p97 is UFMylated on K109 by the E3 UFL1 (UFM1 specific ligase 1) and this modification promotes BECN1 stabilization and assembly of the PtdIns3K complex, suggesting a role for VCP/p97 UFMylation in autophagy initiation. Mechanistically, VCP/p97 UFMylation stabilizes BECN1 through ATXN3 (ataxin 3)-mediated deubiquitination. As a key component of the PtdIns3K complex, stabilized BECN1 facilitates assembly of this complex. Re-expression of VCP/p97, but not the UFMylation-defective mutant, rescued the VCP/p97 depletion-induced increase in MAP1LC3B/LC3B protein expression. We also showed that several pathogenic VCP/p97 mutations identified in a variety of neurological disorders and cancers were associated with reduced UFMylation, thus implicating VCP/p97 UFMylation as a potential therapeutic target for these diseases.

GATA3 functions downstream of BRCA1 to promote DNA damage repair and suppress dedifferentiation in breast cancer.

BACKGROUND: Inadequate DNA damage repair promotes aberrant differentiation of mammary epithelial cells. Mammary luminal cell fate is mainly determined by a few transcription factors including GATA3. We previously reported that GATA3 functions downstream of BRCA1 to suppress aberrant differentiation in breast cancer. How GATA3 impacts DNA damage repair preventing aberrant cell differentiation in breast cancer remains elusive. We previously demonstrated that loss of p18, a cell cycle inhibitor, in mice induces luminal-type mammary tumors, whereas depletion of either Brca1 or Gata3 in p18 null mice leads to basal-like breast cancers (BLBCs) with activation of epithelial-mesenchymal transition (EMT). We took advantage of these mutant mice to examine the role of Gata3 as well as the interaction of Gata3 and Brca1 in DNA damage repair in mammary tumorigenesis. RESULTS: Depletion of Gata3, like that of Brca1, promoted DNA damage accumulation in breast cancer cells in vitro and in basal-like breast cancers in vivo. Reconstitution of Gata3 improved DNA damage repair in Brca1-deficient mammary tumorigenesis. Overexpression of GATA3 promoted homologous recombination (HR)-mediated DNA damage repair and restored HR efficiency of BRCA1-deficient cells. Depletion of Gata3 sensitized tumor cells to PARP inhibitor (PARPi), and reconstitution of Gata3 enhanced resistance of Brca1-deficient tumor cells to PARP inhibitor. CONCLUSIONS: These results demonstrate that Gata3 functions downstream of BRCA1 to promote DNA damage repair and suppress dedifferentiation in mammary tumorigenesis and progression. Our findings suggest that PARP inhibitors are effective for the treatment of GATA3-deficient BLBCs.

The ARID1A-METTL3-m6A axis ensures effective RNase H1-mediated resolution of R-loops and genome stability.

R-loops are three-stranded structures that can pose threats to genome stability. RNase H1 precisely recognizes R-loops to drive their resolution within the genome, but the underlying mechanism is unclear. Here, we report that ARID1A recognizes R-loops with high affinity in an ATM-dependent manner. ARID1A recruits METTL3 and METTL14 to the R-loop, leading to the m6A methylation of R-loop RNA. This m6A modification facilitates the recruitment of RNase H1 to the R-loop, driving its resolution and promoting DNA end resection at DSBs, thereby ensuring genome stability. Depletion of ARID1A, METTL3, or METTL14 leads to R-loop accumulation and reduced cell survival upon exposure to cytotoxic agents. Therefore, ARID1A, METTL3, and METTL14 function in a coordinated, temporal order at DSB sites to recruit RNase H1 and to ensure efficient R-loop resolution. Given the association of high ARID1A levels with resistance to genotoxic therapies in patients, these findings open avenues for exploring potential therapeutic strategies for cancers with ARID1A abnormalities.

The Lin28b/Wnt5a axis drives pancreas cancer through crosstalk between cancer associated fibroblasts and tumor epithelium.

Bidirectional signal transduction between tumor epithelial cells and tumor microenvironment (TME) is important for tumor development. Here we show that Lin28b/let-7 pathway is indispensable for modulating the expression of Wnt5a in tumor epithelium, which could be secreted and then up-regulates Lin28b in cancer-associated fibroblasts (CAFs). Moreover, we demonstrate that Lin28b in CAFs promoted growth of PDAC by inducing cytokine PCSK9's production. Using an orthotopic mouse model of PDAC, we find that depletion of Lin28b in CAFs reduced tumor weight, highlighting the importance of Lin28b in PDAC stroma. Thus, our study shows that the Lin28b-Wnt5a axis plays a critical role in bidirectional crosstalk between pancreatic tumor epithelium and TME and results in a pro-|tumorigenic contexture.

PARylated PDHE1α generates acetyl-CoA for local chromatin acetylation and DNA damage repair.

Chromatin relaxation is a prerequisite for the DNA repair machinery to access double-strand breaks (DSBs). Local histones around the DSBs then undergo prompt changes in acetylation status, but how the large demands of acetyl-CoA are met is unclear. Here, we report that pyruvate dehydrogenase 1α (PDHE1α) catalyzes pyruvate metabolism to rapidly provide acetyl-CoA in response to DNA damage. We show that PDHE1α is quickly recruited to chromatin in a polyADP-ribosylation-dependent manner, which drives acetyl-CoA generation to support local chromatin acetylation around DSBs. This process increases the formation of relaxed chromatin to facilitate repair-factor loading, genome stability and cancer cell resistance to DNA-damaging treatments in vitro and in vivo. Indeed, we demonstrate that blocking polyADP-ribosylation-based PDHE1α chromatin recruitment attenuates chromatin relaxation and DSB repair efficiency, resulting in genome instability and restored radiosensitivity. These findings support a mechanism in which chromatin-associated PDHE1α locally generates acetyl-CoA to remodel the chromatin environment adjacent to DSBs and promote their repair.

Keratin 17 Impacts Global Gene Expression and Controls G2/M Cell Cycle Transition in Ionizing Radiation-Induced Skin Damage.

Keratin 17 (K17) is a cytoskeletal protein that is part of the intermediate filaments in epidermal keratinocytes. In K17-/- mice, ionizing radiation induced more severe hair follicle damage, whereas the epidermal inflammatory response was attenuated compared with that in wild-type mice. Both p53 and K17 have a major impact on global gene expression because over 70% of the differentially expressed genes in the skin of wild-type mice showed no expression change in p53-/- or K17-/- skin after ionizing radiation. K17 does not interfere with the dynamics of p53 activation; rather, global p53 binding in the genome is altered in K17-/- mice. The absence of K17 leads to aberrant cell cycle progression and mitotic catastrophe in epidermal keratinocytes, which is due to nuclear retention, thus reducing the degradation of B-Myb, a key regulator of the G2/M cell cycle transition. These results expand our understanding of the role of K17 in regulating global gene expression and ionizing radiation-induced skin damage.

The HDAC6-RNF168 axis regulates H2A/H2A.X ubiquitination to enable double-strand break repair.

Histone deacetylase 6 (HDAC6) mediates DNA damage signaling by regulating the mismatch repair and nucleotide excision repair pathways. Whether HDAC6 also mediates DNA double-strand break (DSB) repair is unclear. Here, we report that HDAC6 negatively regulates DSB repair in an enzyme activity-independent manner. In unstressed cells, HDAC6 interacts with H2A/H2A.X to prevent its interaction with the E3 ligase RNF168. Upon sensing DSBs, RNF168 rapidly ubiquitinates HDAC6 at lysine 116, leading to HDAC6 proteasomal degradation and a restored interaction between RNF168 and H2A/H2A.X. H2A/H2A.X is ubiquitinated by RNF168, precipitating the recruitment of DSB repair factors (including 53BP1 and BRCA1) to chromatin and subsequent DNA repair. These findings reveal novel regulatory machinery based on an HDAC6-RNF168 axis that regulates the H2A/H2A.X ubiquitination status. Interfering with this axis might be leveraged to disrupt a key mechanism of cancer cell resistance to genotoxic damage and form a potential therapeutic strategy for cancer.

SMYD2 inhibition-mediated hypomethylation of Ku70 contributes to impaired nonhomologous end joining repair and antitumor immunity.

DNA damage repair (DDR) is a double-edged sword with different roles in cancer susceptibility and drug resistance. Recent studies suggest that DDR inhibitors affect immune surveillance. However, this phenomenon is poorly understood. We report that methyltransferase SMYD2 plays an essential role in nonhomologous end joining repair (NHEJ), driving tumor cells adaptive to radiotherapy. Mechanically, in response to DNA damage, SMYD2 is mobilized onto chromatin and methylates Ku70 at lysine-74, lysine-516, and lysine-539, leading to increased recruitment of Ku70/Ku80/DNA-PKcs complex. Knockdown of SMYD2 or its inhibitor AZ505 results in persistent DNA damage and improper repair, which sequentially leads to accumulation of cytosolic DNA, and activation of cGAS-STING pathway and triggers antitumor immunity via infiltration and activation of cytotoxic CD8+ T cells. Our study reveals an unidentified role of SMYD2 in regulating NHEJ pathway and innate immune responses, suggesting that SMYD2 is a promising therapeutic target for cancer treatment.

Loss of function of GATA3 regulates FRA1 and c-FOS to activate EMT and promote mammary tumorigenesis and metastasis.

Basal-like breast cancers (BLBCs) are among the most aggressive cancers, partly due to their enrichment of cancer stem cells (CSCs). Breast CSCs can be generated from luminal-type cancer cells via epithelial-mesenchymal transition (EMT). GATA3 maintains luminal cell fate, and its expression is lost or reduced in BLBCs. However, deletion of Gata3 in mice or cells results in early lethality or proliferative defects. It is unknown how loss-of-function of GATA3 regulates EMT and CSCs in breast cancer. We report here that haploid loss of Gata3 in mice lacking p18Ink4c, a cell cycle inhibitor, up-regulates Fra1, an AP-1 family protein that promotes mesenchymal traits, and downregulates c-Fos, another AP-1 family protein that maintains epithelial fate, leading to activation of EMT and promotion of mammary tumor initiation and metastasis. Depletion of Gata3 in luminal tumor cells similarly regulates Fra1 and c-Fos in activation of EMT. GATA3 binds to FOSL1 (encoding FRA1) and FOS (encoding c-FOS) loci to repress FOSL1 and activate FOS transcription. Deletion of Fra1 or reconstitution of Gata3, but not reconstitution of c-Fos, in Gata3 deficient tumor cells inhibits EMT, preventing tumorigenesis and/or metastasis. In human breast cancers, GATA3 expression is negatively correlated with FRA1 and positively correlated with c-FOS. Low GATA3 and FOS, but high FOSL1, are characteristics of BLBCs. Together, these data provide the first genetic evidence indicating that loss of function of GATA3 in mammary tumor cells activates FOSL1 to promote mesenchymal traits and CSC function, while concurrently repressing FOS to lose epithelial features. We demonstrate that FRA1 is required for the activation of EMT in GATA3 deficient tumorigenesis and metastasis.

Protocol to purify the histone deacetylase SIRT6 and assess its activity in vitro.

The histone deacetylase known as sirtuin 6 (SIRT6) deacetylates both histone and non-histone proteins but has low deacetylase activity in vitro. Here, we present a protocol to monitor SIRT6-mediated deacetylation of long-chain acyl-CoA synthase 5 in the presence of palmitic acid. We describe the purification of His-SIRT6 and a Flag-tagged substrate. We then detail a deacetylation assay protocol that can be widely applied to study other SIRT6-mediated deacetylation events and the effect of SIRT6 mutations on its activity. For complete details on the use and execution of this protocol, please refer to Hou et al. (2022).1.

Compensatory classification in spine sagittal malalignment with lumbar degeneration.

OBJECTIVE: To generate a compensatory classification to evaluate sagittal spinal malalignment with lumbar degeneration. METHODS: We included 162 patients with low back pain who underwent full-length spinal radiography in our hospital from August 2019 to October 2021. Using full-length spine X-rays, we measured pelvic tilt (PT), sacral slope (SS), pelvic incidence (PI), thoracic kyphosis (TK), lumbar lordosis (LL), C7 slope (C7S), thoracolumbar kyphosis (TLK), and C7 sagittal vertical axis (SVA). We also recorded the Oswestry Disability Index (ODI) and visual analog scale (VAS). Patients were divided into four groups based on the SRS-Schwab classification and four other groups based on the compensatory classification. RESULTS: ODI correlated with age, SS, LL, TK, C7-SVA, SRS-Schwab classification, and compensatory classification. Lumbar VAS score correlated with LL, TK, C7-SVA, SRS-Schwab classification, and compensatory classification. Leg VAS score only correlated with LL. Hidden imbalance and imbalance with compensation had more significant PT and larger TK than balance patients. The symptoms of the four compensatory classification groups gradually worsened. CONCLUSION: The spinal-pelvic sagittal balance in patients with lumbar degeneration based on pelvic and thoracic compensation can reflect spinal balance and symptoms. This parameter might help evaluate spine sagittal alignment in elderly patients with lumbar degeneration.

Cervical sagittal alignment changes following anterior cervical discectomy and fusion, laminectomy with fusion, and laminoplasty for multisegmental cervical spondylotic myelopathy.

OBJECTIVE: Cervical sagittal alignment changes (CSACs) influence outcomes and health-related quality-of-life. Anterior cervical discectomy and fusion (ACDF), laminectomy with fusion (LCF), and laminoplasty (LP) are common treatments for multisegmental cervical spondylotic myelopathy; however, these approaches need to be compared. METHODS: Our study included 167 patients who underwent ACDF, LCF, or LP. Patients were divided into four groups according to C2-C7 Cobb angle (CL): kyphosis (CL < 0°), straight (0° ≤ CL < 10°), lordosis (10° ≤ CL < 20°), and extreme lordosis (20° ≤ CL) groups. CSACs consist of two parts. CSAC from the preoperative period to the postoperative period is surgical correction change (SCC). CSAC from the postoperative period to the final follow-up period is postoperative lordosis preserving (PLP). Outcomes were evaluated using the Japanese Orthopaedic Association score and the neck disability index. RESULTS: ACDF, LCF, and LP had equivalent outcomes. ACDF had greater SCC than LCF and LP. During follow-up, lordosis decreased in the ACDF and LCF groups but increased in the LP group. For straight alignment, ACDF had greater CSAC and greater SCC than the LCF and LP groups but similar PLP. For lordosis alignment, ACDF and LP had positive PLP, and LCF had negative PLP. For extreme lordosis, ACDF, LP, and LCF had negative PLP; however, cervical lordosis in the LP group was relatively stable during follow-up. CONCLUSIONS: ACDF, LCF, and LP have different CSAC, SCC, and PLP according to a four-type cervical sagittal alignment classification. Preoperative cervical alignment is an important consideration in deciding the type of surgical treatment in CSM.

The effect of interlaminar Coflex stabilization in the topping-off procedure on local and global spinal sagittal alignment.

PURPOSE: To investigate the effect of interlaminar Coflex stabilization (ICS) at various segments in the topping-off procedure on local and global spinal sagittal alignment. METHODS: Eighty-nine consecutive patients with degenerative lumbar spinal stenosis (DLSS) who underwent ICS and transforaminal lumbar interbody fusion (TLIF) were retrospectively reviewed. They were divided into Group A (L4-L5 ICS + L5-S1 TLIF), Group B (L3-L4 ICS + L4-S1 TLIF), and Group C (L2-L3 ICS + L3-S1 TLIF) according to their fusion levels. The measured local sagittal parameters included the implanted segmental angle (ISA), intervertebral disc angle (IDA), intervertebral foreman height (IFH), and disc height. The assessed global sagittal parameters included thoracic kyphosis, lumbar lordosis (LL), the fused segment angle (FSA), the sacral slope, the pelvic tilt, pelvic incidence, and the sagittal vertical axis. The Oswestry Disability Index (ODI) and visual analog scales (VAS) were recorded to evaluate the clinical outcomes. RESULTS: Regarding the local alignment parameters, the ISA and IDA decreased immediately after surgery in Groups A and B, followed by an increase at the last follow-up (all, P < 0.05). Conversely, the IFH of Groups A and B first increased after surgery and then decreased to approximately the original value (all, P < 0.05). No significant differences were evident between the local sagittal parameters at different time points in Group C. Regarding the global sagittal profiles, the LL and FSA exhibited a significant postoperative increase (both at P < 0.05) in all the groups. All three groups displayed significant improvements in the ODI, VAS-back pain, and VAS-leg pain. Furthermore, 4.5% (4/89) of the patients exhibited radiographic adjacent segment degeneration (ASD) at the last follow-up. CONCLUSION: ICS during topping-off surgery led to a temporary loss of local lordosis, especially in the lower lumbar segment, while the intervertebral space realigned after middle-term follow-up. The topping-off procedure with ICS is a feasible and promising surgical option of DLSS since it reduces fusion levels and prevents ASD development.

KAT8 acetylation-controlled lipolysis affects the invasive and migratory potential of colorectal cancer cells.

Epigenetic mechanisms involved in gene expression play an essential role in various cellular processes, including lipid metabolism. Lysine acetyltransferase 8 (KAT8), a histone acetyltransferase, has been reported to mediate de novo lipogenesis by acetylating fatty acid synthase. However, the effect of KAT8 on lipolysis is unclear. Here, we report a novel mechanism of KAT8 on lipolysis involving in its acetylation by general control non-repressed protein 5 (GCN5) and its deacetylation by Sirtuin 6 (SIRT6). KAT8 acetylation at K168/175 residues attenuates the binding activity of KAT8 and inhibits the recruitment of RNA pol II to the promoter region of the lipolysis-related genes adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL), subsequently down-regulating lipolysis to affect the invasive and migratory potential of colorectal cancer cells. Our findings uncover a novel mechanism that KAT8 acetylation-controlled lipolysis affects invasive and migratory potential in colorectal cancer cells.

Assessing SIRT7 Activity In Vivo and In Vitro in Response to DNA Damage.

The class III histone deacetylase (HDACs) also known as sirtuins (SIRTs 1-7) are ubiquitously expressed, but SIRT7 mainly resides as nucleolar protein. In this chapter a couple of methods are described that are used to detect modulation of SIRT7 in response to DNA damage. SIRT7 is localized in the nucleoli and binds to the chromatin after DNA damage. Therefore, a protocol was optimized by our lab for chromatin fractionation. By this method, the movement of SIRT7 can be detected from the soluble part (cytosol+nucleoplasm) to the solid part (chromatin) of the cell. Change of SIRT7 expression levels, in different cells or after different treatment, can be detected by isolating whole-cell lysate followed by Western blotting. For analyzing binding of SIRT7 to other substrates, we have also optimized manual immunoprecipitation assays by using 1% NP40 buffer. This protocol is very helpful to pull down SIRT7 and associated proteins by using a single buffer. SIRT7 is a deacetylase, and its deacetylation activity can be checked both inside the cell by in vivo deacetylation assay and outside the cell by in vitro deacetylation assays. Recently it was also discovered that SIRT7 has desuccinylase activity which can be detected by histone desuccinylation assay. This chapter provides the methodology of SIRT7 detection in the whole cell lysate, binding of SIRT7 to the chromatin and other proteins for performing deacetylation and desuccinylation activity.

The repression of oncoprotein SET by the tumor suppressor p53 reveals a p53-SET-PP2A feedback loop for cancer therapy.

The oncoprotein SET is frequently overexpressed in many types of tumors and contributes to malignant initiation and progression through multiple mechanisms, including the hijacking of the tumor suppressors p53 and PP2A. Targeting aberrant SET represents a promising strategy for cancer intervention. However, the mechanism by which endogenous SET is regulated in cancer cells remains largely unknown. Here, we identified the tumor suppressor p53 as a key regulator that transcriptionally repressed the expression of SET in both normal and cancer cells. In addition, p53 stimulated PP2A phosphatase activity via p53-mediated transcriptional repression of SET, whereby SET-mediated inhibition of PP2A was alleviated. Moreover, targeting the interaction between SET and PP2A catalytic subunit (PP2Ac) with FTY720 enhanced stress-induced p53 activation via PP2A-mediated dephosphorylation of p53 on threonine 55 (Thr55). Therefore, our findings uncovered a previously unknown p53-SET-PP2A regulatory feedback loop. To functionally potentiate this feedback loop, we designed a combined therapeutic strategy by simultaneously administrating a p53 activator and SET antagonist in cancer cells and observed a dramatic synergistic effect on tumor suppression. Our study reveals mechanistic insight into the regulation of the oncoprotein SET and raises a potential strategy for cancer therapy by stimulating the p53-SET-PP2A feedback loop.

Structure-Based Discovery of Selective Histone Deacetylase 8 Degraders with Potent Anticancer Activity.

Inducing protein degradation by proteolysis targeting chimeras has gained tremendous momentum as a promising novel therapeutic strategy. Here, we report the design, synthesis, and biological characterization of highly potent proteolysis targeting chimeric small molecules targeting the epigenetic regulator histone deacetylase 8 (HDAC8). We developed potent and effective HDAC8 degraders, as exemplified by SZUH280 (16e), which effectively induced HDAC8 protein degradation and inhibited cancer cell growth even at low micromolar concentrations. Our preliminary mechanistic studies revealed that SZUH280 hampers DNA damage repair in cancer cells, promoting cellular radiosensitization. In mice, a single SZUH280 dose induced rapid and prolonged HDAC8 protein degradation in xenograft tumor tissues. Moreover, SZUH280 alone or in combination with irradiation resulted in long-lasting tumor regression in an A549 tumor mouse model. Our findings qualify a new chemical tool for HDAC8 knockdown and may lead to the development of a new class of cancer therapeutics.

Four types of global spine sagittal alignment and compensation mechanism in adult patients with lumbar degenerative disease.

BACKGROUND: The objective of this study was to describe and classify common variations and compensation mechanisms in the sagittal alignment of the spine with lumbar degenerative disease. METHODS: A total of 230 patients over 18 years old who underwent whole-spine X-rays to evaluate lower back pain were enrolled in this study. C7 slope, pelvic tilt (PT), sacral slope (SS), pelvic incidence (PI), thoracic kyphosis (TK), lumbar lordosis (LL), cervical lordosis (CL), thoracolumbar kyphosis (TLK), and sagittal vertical axis (SVA) were measured. Patients were divided into Group A (balance without compensation), B (balance with compensation), C (unbalance with compensation), and D (unbalance without compensation) according to spinopelvic balance and thoracic compensation. RESULTS: Group A had the largest LL, smallest PT, largest SS, and best clinical parameters of the four groups (p < 0.001, p < 0.001, p < 0.001, p < 0.001). The age increased gradually from Group B to Group D. Group B had an increased TK compared with Group A (p < 0.001). Group C had an increased TK compared with Group A (p < 0.001). Group D had an increased C7 slope compared with Group A (p = 0.022). CONCLUSIONS: This classification is shown four different regional and global alignments of the spine. Compensation took place to keep the balance of the spine. Classification types were consistent with age, compensation abilities, and clinical parameters. This classification potentially represents a valuable tool for comprehensive analysis of lumbar degenerative before surgical treatment considering sagittal balance.

Impact of cervical and global spine sagittal alignment on cervical curvature changes after posterior cervical laminoplasty.

OBJECTIVE: To analyze the correlation between the changes in cervical curvature and the sagittal parameters of spino-pelvic and clinical efficacy after posterior laminoplasty (LP). METHODS: The patients with cervical spondylosis treated with LP from June 2018 to December 2020 were reviewed. The preoperative and follow-up spine full-length films were measured. The measured data included C2-C7 Cobb angle, C2-7 sagittal vertical axis (SVA), T1 slope (T1S), pelvic incidence, sacral slope (SS), pelvic tilt (PT), lumbar lordosis (LL), thoracic kyphosis (TK), and C7-SVA. Japanese Orthopaedic Association (JOA) score and neck disability index (NDI) score were recorded before surgery and follow-up. RESULTS: There were 56 patients in this study. There were no significant differences in spino-pelvic sagittal parameters before and after surgery; however, the JOA score significantly improved. The changes in postoperative cervical lordosis correlated with SS, PT, LL, T1S, and C7-SVA (P < 0.05). Regression analysis showed that T1S and C7-SVA were associated with reducing cervical lordosis (P = 0.021 and P = 0.001, respectively). Patients with larger T1S combined with larger C7-SVA had more cervical lordosis loss, poor JOA improvement, and high postoperative NDI scores (P < 0.001, P = 0.018, and P < 0.001, respectively). CONCLUSION: Patients should be examined with full-length spine film before surgery to evaluate the cervical and spino-pelvic sagittal balance. T1S and C7-SVA correlated with changes in cervical sagittal alignment after LP. LEVEL OF EVIDENCE: III.