The MicroRNA hsa-let-7g Promotes Proliferation and Inhibits Apoptosis in Lung Cancer by Targeting HOXB1

PURPOSE: The goal of this study was to explore the effects of hsa-let-7g on cell proliferation and apoptosis, and elucidate its role in lung cancer development.MATERIALS AND METHODS: The expression levels of has-let-7g and HOXB1 in tissues and cells were measured by qRT-PCR. An inhibitor of hsa-let-7g or one targeting a control messenger RNA were transfected into A549 and H1944 lung cancer cells, and the effects of hsa-let-7g dysregulation on cell viability and apoptosis were analyzed using CCK-8 and apoptosis detection assays. HOXB1 was confirmed as the target gene of hsa-let-7g, based on luciferase reporter assay results. The relationship between hsa-let-7g and HOXB1 was confirmed by co-transfection of inhibitors of hsa-let-7g and HOXB1 followed by Western blot, CCK-8, and apoptosis detection assays.RESULTS: We observed high expression of hsa-let-7g in lung cancer tissues compared to the corresponding normal tissues, and generally higher expression of hsa-let-7g in patients with advanced tumor classification. The results of CCK-8 and apoptosis detection experiments showed that the inhibition of hsa-let-7g significantly inhibited proliferation of A549 and H1944 cells, but also promoted apoptosis. HOXB1 is a specific target of hsa-let-7g, and downregulation of HOXB1 in lung cancer cells reversed the suppressive effects caused by knocking down hsa-let-7g.CONCLUSION: These data collectively suggest that the expression of hsa-let-7g inhibits lung cancer cells apoptosis and promotes proliferation by down-regulating HOXB1. The results from this study demonstrate the potential of hsa-let-7g/HOXB1 axis as a therapeutic target for the treatment of lung cancer.

Efficiency analysis on functional protection of nerve plane-oriented laparoscopic total mesorectal excision / 中华胃肠外科杂志

Objective@#Using previous total mesorectal excision with pelvic autonomic nerve preservation (PANP+TME) and simple total mesorectal excision (TME) without emphasis on retained nerves as control, we explore the advantages of nerve plane-oriented laparoscopic total mesorectal excision (NPO+LTME) on urinary and sexual function.@*Methods@#A retrospective cohort study was carried out. Case inclusion criteria: (1) male patients with pathologically confirmed middle and low rectal adenocarcinoma (4 to 11 cm from the anus); (2) stage T1-2tumor; (3) normal sexual life before operation. Exclusion criteria: (1) no pathological diagnosis before surgery; (2) local recurrence or distant metastasis; (3) preoperative neoadjuvant chemoradiotherapy; (4) opensurgery and laparoscopic surgery conversionto open; (5) no follow-up data. According to the above criteria, clinical data of 173 male patients with low and middle rectal adenocarcinoma who underwent radical operation for laparoscopic rectal cancer from July 2003 to July 2018 at the Department of Gastrointestinal Surgery, Wuhan University People′s Hospital were collected. According to different surgical methods, patients were divided into TME group (58 cases), PANP+TME group (63 cases) and NPO+LTME group (52 cases). There were no significant differences in the baseline data including age, body mass index and pathological examination between the 3 groups (all P>0.05). The nerve plane referred to the nerve, the adipose tissue, the extremely finecapillaries around the nerve with overlying fine membranous tissue. NPO+LTME referred to the process of laparoscopic TME guided by the nerve plane, performing in the loose connective tissue between the nerve plane and the rectal properfascia, in order to ensure the integrity of the nerve plane, and maximally protect the patient's urinary and reproductive functions. The operation time, intraoperative blood loss, urinary catheter removal time, urinary function grading, postoperative first erection time, and erectile function and ejaculation function were observed and compared among the 3 groups at 3- and 6-month after operation.@*Results@#In the NPO+LTME group, the PANP+TME group and the TME group, the operation time was (181.9±24.5) minutes, (176.7±29.2) minutes and (137.7±16.2) minutes, respectively (F=54.868, P<0.001); the intraoperative blood lost was (6.0±1.4) ml, (6.5±1.8) ml and (12.8±4.6) ml, respectively (F=95.016, P<0.001); the time to postoperative removal of the catheter was (2.4±1.1) days, (3.7 ±1.7) days and (6.5±2.4) days, respectively (F=79.409, P<0.001); the first postoperative erection time was (1.6±0.6) days, (8.9±2.7) days and (15.9±6.8) days (F=177.677, P<0.001), respectively, whose differences were all statistically significant (all P<0.01). In comparison of urinary function grading, the proportion of grade I (normal function, no urinary dysfunction) in the NPO+LTME, the ANP+TME group and the TME group was 84.1% (53/63), 39.7% (23/58) and 19.2% (10/52), respectively, and the difference was statistically significant (H=52.915, P<0.001). At postoperative 3- and 6-month, proportion of patients with grade I erectile function (normal erectile function) was 77.8% (49/63) and 85.7% (54/63), 44.8% (26/58) and 53.4% (31/58), 28.8% (15/52) and 48.1% (25/52) in the NPO+LTME group, the PANP+TME group, and the TME group, respectively. The differences were statistically significant (H=91.709, P<0.001; H=79.692, P<0.001). The proportion of patients with grade I ejaculation function (with ejaculation, no abnormalities in routine semen examination before and after surgery) at 3- and 6-month after surgery in the NPO+LTME group, the PANP+TME group and the TME group was 82.5% (52/63) and 87.3% (55/63), 53.4% (31/58) and 60.3% (35/58), 28.8% (15/52) and 46.1% (24/52), respectively. The differences were statistically significant as well (H=86.543, P<0.001; H=78.667, P<0.001). Patients in the NPO+LTME group had no grade III erections and ejaculation disorders.@*Conclusion@#The surgical procedure of NPO+LTME can promote the recovery of postoperative neurological function and preserve urination and sexual function better.