Rectal Cancer Cells Research Articles

Interferon-inducible CXC-chemokines are crucial immune modulators and survival predictors in colorectal cancer.

Tumor-infiltrating T-cells are strongly associated with prognosis in colorectal cancer, but the mechanisms governing intratumoral lymphocyte recruitment are unclear. We investigated the clinical relevance and functional contribution of interferon-regulated CXC-chemokines CXCL9, CXCL10, and CXCL11, described as T-cells attractants. Their expression was significantly elevated in tumors as compared to normal colon in 163 patients with colon cancer, represented an independent positive predictor of post-operative survival, and was highly significantly correlated with the presence of tumor-infiltrating cytotoxic CD8+ T-cells and CD4+ TH1-effector cells. The regulation of chemokine expression was investigated in established cell lines and in tissue explants from resected tumor specimen (n=22). All colorectal cancer cell lines tested, as well as stroma or endothelial cells, produced CXC-chemokines in response to cytokine stimulation. Moreover, resected tumor explants could be stimulated to produce CXC-chemokines, even in cases with initially low CXC-levels. Lastly, a causative role of chemokine expression was evaluated with an orthotopic mouse model, based on isogenic rectal CT26 cancer cells, engineered to express CXCL10. The orthotopic model demonstrated a protective and anti-metastatic role of intratumoral CXCL10 expression, mediated mainly by adaptive immunity.

Abstract 4760: Wnt/β-catenin signaling mediates resistance of colorectal cancer cell lines to chemoradiotherapy

Abstract Background: Activation of Wnt/β-catenin signaling plays a central role in the development and progression of colorectal cancer (CRC). Previously, we demonstrated that the Wnt transcription factor TCF7L2 was overexpressed in primary rectal cancers that were resistant to chemoradiotherapy (CRT), and that TCF7L2 functionally mediates resistance of CRC to clinically relevant doses of CRT. However, it remained unclear whether the resistance was mediated by a TCF7L2 inherent mechanism or Wnt/β-catenin signaling in general. Methods: We silenced another key-component of canonical Wnt-signaling, CTNNB1 (β-catenin) in rectal cancer cell lines LS1034, SW480, and SW837 by RNAi. Afterwards cells were exposed to varying doses of irradiation (+/- 5 FU) to assess the influence of β-catenin on radiation response. Activation of Wnt-signaling in “normal” epithelial cells (retina pigment epithelial cells RPE) was achieved either by stimulation with Wnt-3A, or stable overexpression of non-degradable β-catenin (S33Y-mutated) and confirmed by a dual luciferase reporter assay. Changes in radio-(chemo-) sensitivity were analyzed again by a colony formation assay. SW1463 were repeatedly irradiated (68Gy) to establish an isogenic radio-resistant cell line. Gene-expression profiles, without or 6h after a single dose of 4Gy, of RPE cells expressing a control vector or overexpressing β-catenin and radioresistant or wildtype SW1463 cells were established using micro Arrays. Results: Silencing of CTNNB1 resulted in (chemo-) radiation-sensitization of all three CRC-cell lines. To further investigate the potential role of Wnt/β-catenin signaling in controlling therapeutic responsiveness, non-tumorigenic RPE cells were stimulated with Wnt-3A, which significantly increased resistance to CRT. This effect could be recapitulated by overexpression of β-catenin (S33Y-mut.), resulting in a significantly increased resistance to CRT. The effect could be rescued by siRNA mediated knockdown of β-catenin. Consistent with these findings, we observed higher expression levels of active (unphosphorylated) β-catenin as well as increased TCF reporter activity in SW1463 cells that were rendered radiation-resistant due to repeated IR treatment. Gene expression profiling of radioresistant and wildtype SW1463 as well as RPE cells overexpressing β-catenin or a control vector revealed significant transcriptomal changes. Most interestingly the resistant cells (radioresistant SW1463 and RPE overexpressing β-catenin) reacted with differential activation of metabolic, inflammatory, cell survival and cell cycle pathways to irradiation. Conclusion: Together, these findings strongly support the interpretation that Wnt/β-catenin signaling plays a central role in mediating resistance of CRC cells to CRT by deregulating essential pathways. Hence, pathway inhibition may represent a promising strategy to increase therapeutic responsiveness to CRT. Citation Format: Georg Emons, Melanie Spitzner, Sebastian Reineke, Noam Auslander, Frank Kramer, Margret Rave-Fraenk, Jochen Gaedcke, Michael Ghadimi, Thomas Ried, Marian Grade. Wnt/β-catenin signaling mediates resistance of colorectal cancer cell lines to chemoradiotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4760. doi:10.1158/1538-7445.AM2017-4760

Preparation and in vitro and in vivo release of ALA and HMME hydrogel suppository

Objective To prepare 5-aminolevulinic acid (ALA) and hematoporphyrin monomethyl ether (HMME) hydrogel suppositories and to evaluate their photosensitizer transfer efficiencies in rectal tumor tissue. Methods The BALB/c mice implanted SW837 rectal cancer cells subcutaneously were randomly divided into four groups: intrarectal suppository administration group, cutaneous administration group, intratumoral injection group and intravenous injection group. Fluorescence spectrophotometry was used to measure the concentration of protoporphyrin Ⅸ (PpⅨ) and HMME in rectal wall, skin and tumor tissue. The distribution of photosensitizer was determined by a fluorescence spectroscopy system. Results The concentration of PpⅨ in the ALA suppository administration group was 9.76 times (1 h) and 5.80 times (3 h) higher than that in the cutaneous administration group, and the differences were statistically significant (all P<0.05). The maximal penetration depth of ALA in tumor tissue was about 3-6 mm at 2 h after the cutaneous administration. After the HMME suppository administration, the concentration of HMME in the rectal wall was very low. The maximal penetration depth of HMME in tumor tissue was less than 2 mm after the cutaneous administration. Conclusions ALA is more likely to penetrate mucosal barrier compared to skin tissue. The hydrogel suppository based rectal administration is expected to be a new administration method for the rectal cancer photodynamic therapy using ALA. Key words: Photosensitizer; Drug delivery; Photodynamic therapy; HMME; ALA; Rectal cancer

Effect of resveratrol in regulating proliferation and apoptosis of rectal cancer cells via up-regulating PTEN

To analysis the relative expression of PTEN(phosphatase and tensin homology deleted on chromosome ten) in rectal cancer cell lines and the effects of resveratrol on cell proliferation and apoptosis of rectal cancer cells in vitro. Western blot was used to assess the protein expression of PTEN in rectal cancer cell lines and non-malignant colon epithelial cell line. After treating human rectal cancer cell line SW480 with different concentrations of resveratrol, the cellular proliferation was detected by cell counting Kit-8(CCK-8) assay. The apoptotic rate was analyzed by flow cytometry. The protein expressions of Caspase-3, PTEN, p53 and phosphorylase AKT(p-AKT) were detected by Western blot. shRNA(short hairpin RNA) was built to down-regulate PTEN expression in SW480 cells, and detect whether the own-regulated PTEN expression impact resveratrol's effect in growth inhibition and apoptosis induction of in vitro rectal cancer cells. Our results demonstrated that the relative level of PTEN was markedly decreased in Caco-2 and SW480, with statistically significant differences(P<0.001). Resveratrol inhibited the proliferation of rectal cancer cells markedly, and triggered apoptosis of SW480 cells. The protein expressions of Caspase-3, PTEN and p53 were all increased after being treated with resveratrol, while the expression of p-AKT was decreased after the treatment. The expression of endogenous PTEN was significantly decreased in shRNA PTEN-infected SW480 cells. Meanwhile, shRNA PTEN could obviously reduce SW480 cells' anti-proliferative and apoptotic effects. The experimental results suggested that resveratrol can be used as an anti-proliferative and apoptosis induction agent in rectal cancer through up-regulation of PTEN.

1020 - Cancer Associated Fibroblasts Mediate Resistance to Radiotherapy in Rectal Cancer Cells

1020 - Cancer Associated Fibroblasts Mediate Resistance to Radiotherapy in Rectal Cancer Cells

HNRNPLL, a newly identified colorectal cancer metastasis suppressor, modulates alternative splicing of CD44 during epithelial-mesenchymal transition

ObjectiveDespite the recent advances in treatment of colon cancer, the prognosis is unfavourable for patients with distant metastases. The aim of this study was to identify targets for prevention and/or...

YAP Inhibits the Apoptosis and Migration of Human Rectal Cancer Cells via Suppression of JNK-Drp1-Mitochondrial Fission-HtrA2/Omi Pathways

Background/Aims: The Hippo-Yap pathway is associated with tumor development and progression. However, little evidence is available concerning its role in cancer cell apoptosis and migration via mitochondrial homeostasis. Here, we identify mitochondrial fission as a regulator of the Hippo–Yap pathway in human rectal cancer tumorigenesis and metastasis. Methods: In this study, we performed loss-of function assays concerning Yap in RCC via shRNA. Cellular viability and apoptosis were measured via MTT, the TUNEL assay and trypan blue staining. Mitochondrial function was assessed via JC1 staining, the mPTP opening assay, mitochondrial respiratory function analysis, electron microscopy and immunofluorescence analysis of HtrA2/Omi. Mitophagy and mitochondrial fission were assessed via western blots and immunofluorescence. Cell migration was evaluated via the Transwell assay, wound-healing assay and immunofluorescence analysis of F-actin. The interaction between JNK and Yap was detected via co-immunoprecipitation and Yap recombinant mutagenic plasmid transfection. Western blots were used to analyze signaling pathways in conjunction with JNK inhibitors or HtrA2/Omi siRNA. Results: Yap is upregulated in human rectal cancer cells, where its expression correlates positively with cell survival and migration. Functional studies established that silencing of Yap drove JNK phosphorylation, which induced Drp1 activation and translocation to the surface of mitochondria, initiating mitochondrial fission. Excessive mitochondrial fission mediated HtrA2/Omi leakage from the mitochondria into the cytoplasm, where HtrA2/Omi triggered cellular apoptosis via the mitochondrial apoptosis pathway. Moreover, released HtrA2/Omi also phosphorylated cofilin and inhibited cofilin-mediated F-actin polymerization. F-actin collapse perturbed lamellipodia formation and therefore impaired cellular migration and invasion. Conclusion: Collectively, our results demonstrate that Hippo-Yap can serve as a tumor promoter in human rectal cancer and acts by restricting JNK/Drp1/mitochondrial fission/ HtrA2/Omi, with potential implications for new approaches to human rectal cancer therapy.

Study of the effect of LIG4 on the radiosensitivity enhancement of rectal cancer cells by curcumin

To investigate the function of repair gene LIG4 in radiosensitivity enhancement of rectal cancer cells by curcumin. Human rectal cancer cells HT-29 were cultured in normal. LIG4-overexpression HT-29 cells and blank control plasmid HT-29 cells were established by gene transfection. Both kind of HF-29 cells were further randomly divided into curcumin group, radiotherapy group, curcumin plus radiotherapy group (combined group) and control group. The growth inhibition and apoptosis of cells were detected by MTT and Annexin V/PI respectively. Change of tumor volume was observed in nude mouse xenograft model, and the apoptosis of tumor cells was analyzed by TUNEL. Regarding blank control plasmid HT-29 cells, the growth inhibition rate and apoptosis rate in combined group were significantly higher than those in radiotherapy group(all P<0.05); tumor volume of nude mouse in combined group was significantly smaller than that in radiotherapy group, and the apoptotic index in combined group was significantly higher than that in radiotherapy group (all P<0.05). However, regarding LIG4-overexpression HT-29 cells, the growth inhibition rate and apoptosis rate were not significantly different between combined group and radiotherapy group(all P>0.05); the tumor volume of nude mouse and the apoptotic index were also not significantly different between combined group and radiotherapy group (all P>0.05). Down-regulation of LIG4 is an important mechanism of radiosensitivity enhancement of rectal cancer cells by curcumin.

NOX2-ROS-HIF-1α signaling is critical for the inhibitory effect of oleanolic acid on rectal cancer cell proliferation

Rectal cancer is the second leading cause of cancer mortality in the western countries and accounts for 10% incidence and mortality of cancer in the whole world. Drug resistance and severe toxicity severely limited the efficiency of chemotherapy of rectal cancer. Oleanolic acid (OA) is a natural triterpenoid and an aglycone of many saponins. In the present study, we aimed to investigate the effect of OA on rectal cancer cell proliferation and its possible mechanism. We showed that OA concentration-dependently inhibited cell proliferation in HCT-15, HT-29, HCT-8 and Colo 205 human rectal cancer cell lines. OA significantly increased reactive oxygen species (ROS) generation and NADPH oxidase 2 (NOX2) expression in a concentration-dependent manner. In HCT-15 and HT-29 cells, siNOX2 notably suppressed OA-induced ROS generation, inhibition of cell proliferation, increase of S phase cell population and decrease of cyclin D1 and CDK2 expression. OA markedly decreased hypoxia-inducible factor 1α (HIF-1α) expression in HCT-15 and HT-29 cells in a concentration-dependent manner. Overexpression of HIF-1α significantly suppressed OA-induced inhibition of cell proliferation, increase of S phase cell population and decrease of cyclin D1 and CDK2 expression. Inhibition of NOX2 by siRNA notably blocked OA-induced suppression of HIF-1α expression. Our findings provide novel insights into OA-induced inhibition of rectal cancer cell proliferation and highlight NOX2/ROS/HIF-1α axis as a novel therapeutic target for the treatment of rectal cancer.

Robotically Assisted Laparoscopic Ovarian Transposition in Women with Lower Gastrointestinal Cancer Undergoing Pelvic Radiotherapy.

Pelvic radiotherapy (RT) is a standard component of the management for patients with locally advanced rectal cancer or squamous cell carcinoma of the anus. Pelvic RT leads to permanent and irreversible ovarian failure in young women. This study aimed to determine the effectiveness of robotically assisted laparoscopic ovarian transposition (OT) before RT in women with rectal or anal cancer who wanted to preserve normal ovarian function. The study reviewed the medical records of all patients treated at our institution from August 2009 to October 2014 who received robotically assisted laparoscopic OT for rectal or anal cancer before RT. Clinical and hormonal data were abstracted to determine ovarian function. The study identified 22 women with rectal (n=20) or anal (n=2) cancer. The median age of the women was 39years (range 26-45years). For one patient, OT was technically not feasible. The postoperative course was uneventful in all but one case. Follow-up data on ovarian function were unavailable for 3 patients. The median times from RT initiation to the last gynecologic or hormonal evaluation were 9months (range 5-47 months) and 10.5months (range 5-47months), respectively. At the last gynecologic or hormonal follow-up visit, ovarian function was preserved in 12 (67%) of 18 evaluable patients, including 9 (90%) of 10 patients 40years of age or younger and 3 (38%) of 8 patients older than 40years (P=0.07). Robotically assisted laparoscopic bilateral OT is safe and can lead to preservation of ovarian function in two-thirds of patients with low gastrointestinal cancer undergoing pelvic RT. It should be considered in this setting, especially for women age 40years or younger, to avoid premature menopause and its associated sequelae.

Programmed death-ligand 1 expression in rectal cancer.

SummaryBackgroundColorectal cancer (CRC) is the fourth most common cause of death worldwide. Approximately 30 % of all CRC occurs in the rectum. Improvements in survival rates were achieved thanks to multimodal therapy, combining surgery and chemoradiation. Nevertheless, the prognosis of patients suffering from rectal cancer (RC) remains poor. Programmed cell death protein 1 (PD-1) and its ligand programmed death ligand 1 (PD-L1) regulate tumor immune response. The aim of this study was to analyze the expression of PD-L1 in RC pre- and post-neoadjuvant therapy and evaluate PD-L1 as a biomarker and potential target for therapy.MethodsIn all, 29 patients with RC treated at the Medical University Vienna who received preoperative chemoradiation were retrospectively enrolled in this study. Expression of PD-L1 was investigated by immunohistochemistry with two different anti-PD-L1 antibodies.ResultsNo PD-L1 expression on cancer cells could be observed in all 29 cases in the specimens before chemoradiation as well as in the surgical specimens after neoadjuvant therapy. In one of the two staining methods performed, five (17.24 %) post-chemoradiation cases showed faint lymphohistiocytic staining.ConclusionNo expression of PD-L1 in RC cells before and after chemoradiation was found in our collective of 29 patients. Further investigations to evaluate the role of PD-L1 as a potential therapeutic target in RC are urgently needed.

Effect of a chemical inhibitor of human phosphatidylethanolamine-binding protein 4 on radiosensitivity of rectal cancer cells.

BackgroundHuman phosphatidylethanolamine-binding protein 4 (hPEBP4) is a well-established antiapoptosis molecule in recent years. It has also been demonstrated to be involved in the radioresistance of rectal cancer. The objective of this study was to determine whether IOI-42, a chemical inhibitor of hPEBP4, could sensitize rectal cancer cells.MethodsRectal cancer cells were treated with IOI-42 alone or in combination with irradiation. Clonogenic survival assays and tumor volume growth analysis were used, respectively, to study the effect of IOI-42 in vitro and in vivo. Western blot was adopted to measure the activation of signal pathway.ResultsClonogenic survival assays showed that IOI-42, combined with irradiation, caused a significant decrease in colony formation compared with radiation alone, which was associated with the downregulation of Akt activation. And we also confirmed the effect of IOI-42 in nude mice transplanted with human rectal cancer subcutaneously.ConclusionsThese data suggest that IOI-42 has a potential to enhance the radiosensitivity of rectal cancer cells, providing a rationale to further investigate the feasibility of combining of IOI-42 with radiation, keeping in mind that this may result in unexpected toxicities.

Paf15 expression correlates with rectal cancer prognosis, cell proliferation and radiation response.

Paf15, which participates in DNA repair, is overexpressed in numerous solid tumors. Blocking of Paf15 inhibits the growth of many types of cancer cells; while simultaneously enhancing cellular sensitivity to UV radiation. However, its expression and function in rectal cancer (RC) remain unknown. The current study was undertaken to assess the association of Paf15 expression with RC prognosis, as well as to explore the participation of Paf15 in the response of RC cells to irradiation. Increased Paf15 expression was observed in RC tissues and associated with pTNM stage and poor survival. In vitro, Paf15 induced increased RC cell proliferation while accelerating cell cycle progression, inhibiting cell death, and protecting against gamma radiation-induced DNA damage in RC cells. In conclusion, increased Paf15 expression is associated with increased RC proliferation, decreased patient survival, and a worse radiotherapeutic response.

HMGB1 knockdown effectively inhibits the progression of rectal cancer by suppressing HMGB1 expression and promoting apoptosis of rectal cancer cells.

Rectal cancer is a malignant gastrointestinal tumor, which is associated with high morbidity and mortality. High‑mobility group protein 1 (HMGB1) is widely present in the nucleus of eukaryotic cells, and is highly conserved between humans and rodents. Recently, HMGB1 has been reported to be involved in the progression and metastasis of human cancer; however, its role in the development and metastasis of human rectal cancer remains unclear. The present study detected the expression levels of HMGB1 in pathological specimens from patients with clinically identified rectal cancer using immunohistochemistry and western blotting. The results demonstrated that HMGB1 was highly expressed in samples from patients with rectal cancer. The positive rate of HMGB1 in rectal cancer tissues was 96.08% (49/51), which was significantly higher compared with 3.92% (2/51) in normal tissues. In addition, western blotting indicated that HMGB1 was distributed and located not only in the nucleus, but also in the cytoplasm of colorectal cancer cells. HMGB1‑specific short hairpin (sh)RNA was used to silence the endogenous expression of HMGB1 in colorectal cancer cells. A functional assay demonstrated that knockdown of endogenous HMGB1 expression significantly inhibited the proliferation of SW620 and Colo320 cells. Furthermore, western blotting revealed that knockdown of endogenous HMGB1 expression contributed to activation of caspase‑3 and the substrate poly (ADP‑ribose) polymerase. The expression levels of B‑cell lymphoma2 (Bcl‑2) and Bcl‑2‑associated X protein (Bax) were also detected by western blotting. As expected, decreased levels of Bcl‑2 and increased levels of Bax were detected in the HMGB1 shRNA‑transfected colorectal cancer cells, and the Bax/Bcl‑2 ratio was increased in HMGB1 shRNA‑transfected cells. These data indicated that HMGB1 may act as an oncogene in rectal cancer, and knockdown of endogenous HMGB1 expression may significantly inhibit the proliferation of colorectal cancer cells and promote apoptosis of tumor cells. Further research regarding the mechanisms underlying the effects of HMGB1 on the progression of rectal cancer may provide novel targets for the treatment of rectal cancer, and provide a theoretical reference for clinical treatment.

Early marker of DNA damage response, atm, as a predictor of clinical outcome following radiotherapy in rectal cancer patients

Early marker of DNA damage response, atm, as a predictor of clinical outcome following radiotherapy in rectal cancer patients

Histopathology of interspincteric resection specimens of low rectal cancer: An institutional experience of a series of 41 patients

Histopathology of interspincteric resection specimens of low rectal cancer: An institutional experience of a series of 41 patients

Hypoxia facilitates epithelial-mesenchymal transition-mediated rectal cancer progress.

Rectal cancer is a commonly observed tumor in clinics, and epithelial-mesenchymal transition (EMT) is very important for tumor invasion and metastasis. We established a rectal cancer HCT-116 cell hypoxia model and detected cell proliferation, invasion, and EMT-related protein expression in this model, aiming to analyze the effect of hypoxia on rectal cancer cell EMT. Rectal cancer cell line HCT-116 was cultured in normoxic, hypoxic, or anaerobic environment, and hypoxia-inducible factor-1α (HIF-1α) mRNA expression was detected in the cells by real-time PCR. Cell proliferation was tested by MTT assay; cell invasion was determined by transwell assay, and HIF-1α, epithelial-cadherin, and Snail protein levels were evaluated by western blot analysis. HIF-1α mRNA level significantly increased in the anaerobic group compared to that in the normoxic and hypoxic groups (P < 0.05). HCT-116 cell proliferation in the anaerobic group was obviously higher than that in the other two groups, with the hypoxic group showing stronger proliferative ability than the normoxic group (P < 0.05). Compared to the normoxic group, the HCT-116 cells demonstrated enhanced cell invasion and migration in hypoxic and anaerobic groups. HIF-1α and Snail expressions were upregulated, whereas epithelial-cadherin expression had declined in the hypoxic and anaerobic groups, compared to those in the normal control (P < 0.05). Therefore, hypoxia promoted rectal cancer cell progress by increasing HIF-1α to induce EMT.

MOLECULAR GENETIC MARKERS AS PREDICTORS OF TUMOR RESPONSE TO NEOADJUVANT CHEMOTHERAPY FOR RECTAL CANCER

The review presents the mechanisms involved in the biological behavior of rectal cancer cells. The tumor response to neoadjuvant chemoradiotherapy was evaluated. The characteristics of proliferative activity, apoptosis, cell adhesion, and migration of rectal cancer cells influenced by chemotherapy were described. The relationship between molecular genetic markers and prediction of response to chemoradiation in rectal cancer was shown.

Therapy-Induced Cellular Senescence Induces Epithelial-to-Mesenchymal Transition and Increases Invasiveness in Rectal Cancer

IntroductionDNA damaging agents and ionizing radiation used in the therapy of human cancers can induce senescence of cancer cells. Senescent cells exhibit a secretory phenotype (senescence-associated secretome [SAS]) that can affect cancer cell behavior and, eventually, clinical prognosis. We assessed the effects of the SAS on the induction of epithelial-to-mesenchymal transition (EMT) in vitro and in clinical samples from patients with rectal cancer who had undergone neoadjuvant chemoradiotherapy (CRT). Materials and MethodsColorectal cancer cells (HCT 116) were induced into senescence by exposure to either 5-fluorouracil (5-FU) or doxorubicin. The senescent state was confirmed by staining for senescence-associated β-galactosidase (SA-β-Gal). The paracrine effects of SASs were assessed on proliferating HCT 116 cells. The quantified parameters were cell proliferation, invasive capacity, and induction of EMT. Senescence and EMT in clinical samples were assessed by the expression levels (reverse transcriptase-quantitative polymerase chain reaction) of genes related to senescence and EMT after laser-assisted microdissection of cancer cell clusters that stained either positive or negative for SA-β-Gal. ResultsWe have shown that cultured colon cancer cells induced into senescence by exposure to 5-FU exhibit a SAS capable of paracrine induction of EMT in colon and rectal cancer cell lines and increased cell invasion in vitro. Using laser-assisted microdissection, we found that in rectal cancer samples from patients treated with neoadjuvant CRT, tumor cell niches enriched for senescent cells bookmark regions of increased mRNA expression levels of EMT-related proteins (Slug, Snail, vimentin) compared with the nearby senescent-null tumor cell niches. ConclusionWe have provided, first-hand, strongly suggestive evidence that senescent cancer cells emerging in the context of neoadjuvant CRT for rectal cancer influenced the tumor microenvironment by promoting EMT by way of short-range interactions.

MicroRNA‑144 inhibits migration and proliferation in rectal cancer by downregulating ROCK‑1.

Cancer of the colon and rectum are two distinct entities, which require different treatment strategies and separate treatment. MicroRNAs (miRNAs) act as critical regulators of genes involved in several biological processes. Aberrant alterations of miRNAs have been found in several types of cancer, including colon cancer and rectal cancer. Extensive catalogues of downregulated miRNAs have been identified for colon cancer, whereas only limited data are available for rectal cancer. An example of miRNA profiling in a previous study found that miRNA (miR)-144 showed aberrant expression and appeared to be rectal cancer-specific, its expression not being reported in colon cancer. In the present study, the role of miR-144 in rectal cancer was investigated. SW837 and SW1463 cell lines were selected as rectal cell carcinoma cells. Using reverse transcription-quantitative polymerase chain reaction, western blot, BrdU, cell migration and cell viability assays, it was found that the expression levels of miR-144 were significantly reduced in the SW837 and SW1463 cell lines, and the overexpression of miR-144 suppressed rectal cancer cell viability, migration and proliferation. In addition, Rho-associated coiled-coil containing protein kinase 1 (ROCK1) was identified as a target of miR-144 in the rectal cancer cells. The supplementation of ROCK1 markedly restored the cell migration and proliferation, which was inhibited by miR-144. Together, the data of the present study demonstrated that miR-144 acts as a tumor suppressor by targeting ROCK1, and indicates the potential of miR-144 as a novel biomarker and target in the treatment of rectal cancer.