ATF2-Induced Overexpression of lncRNA LINC00882, as a Novel Therapeutic Target, Accelerates Hepatocellular Carcinoma Progression via Sponging miR-214-3p to Upregulate CENPM.

BACKGROUND: Long intergenic non-protein coding RNA 882 (LINC00882) are abnormally expressed in several tumors. Our research aimed to uncover the functions and the potential mechanisms of LINC00882 in hepatocellular carcinoma (HCC) progression. METHODS: RT-qPCR was applied to identify LINC00882 and miR-214-3p levels in HCC specimens and cells. Luciferase reporter was applied for the exploration of whether activating transcription factor 2 (ATF2) could bind to the promoter region of LINC00882. Cell proliferation, invasion, and migration were evaluated. In vivo tumor xenograft models were constructed to assess tumorigenicity. RT-PCR, Western blot and Luciferase reporter assays were conducted to examine the regulatory relationships among LINC00882, miR-214-3p and ATF2. RESULTS: LINC00882 was markedly upregulated in HCC cells and clinical specimens. Additionally, ATF2 could bind directly to the LINC00882 promoter region and activate its transcription. Loss-of-function studies further demonstrated that LINC00882 knockdown inhibited proliferation, invasion, and migration of HCC cells. Mechanistically, LINC00882 adsorbed miR-214-3p, thus promoting the expressions of CENPM. Rescue assays demonstrated that functions of LINC00882 deficiency in HCC cells were reversed through suppressing miR-214-3p. CONCLUSION: Our group identified a novel regulatory axis of ATF2/LINC00882/miR-214-3p/CENPM, which may provide potential therapeutic targets for HCC.

[Genetic analysis in a Chinese deaf-mute family with X linked recessive inheritance].

In studying genetic factors in hearing loss among Chinese hearing-impaired population, a Chinese family with deaf-mute that had been reversion inherited through five generations was found (named pedigree L021). X linked recessive inheritance was hypothesized to be the transmission in this family. A total of 64 members in this family were investigated. Of these, audiometric evaluation was performed on 31 members, including 8 males with deaf-mute. Most affected individuals showed deafness or profound sensorineural hearing loss. Blood samples were obtained from 31 consented individuals in this family. Pedigree analysis indicates a X-linked recessive inheritance pattern in pedigree L021. The pedigree described herein provides an excellent model for further study on the molecular mechanism of congenital deaf-mute.

[Development and evaluation of standardized Mandarin monosyllable audiometric materials].

OBJECTIVE: To develop a set of Mandarin monosyllabic list for the goal to use as a standardized speech recognition assessment tool in China with sufficient validity, reliability and sensitivity. METHODS: Thirty lists were designed based on the following criteria: efficiency, phonemic-balance, familiarity and coverage, while each list was designed corresponding to 25 monosyllables. These lists were read by a male broadcaster, recorded digitally and composed into compact disc. Our work consisted of three phases. Phase I: Sixty adults with normal hearing were recruited from Beijing to repeat as many syllables which they heard as possible. According to the randomized block design, 30 lists were presented with 6 intensities including -1 dB, 5 dB, 11 dB, 15 dB, 21 dB and 27 dB HL(speech). The lists and intensities were counterbalanced across all participants. Recognition scores in individual intensities for each list were calculated, and then logistic regression was utilized to fit Performance-Intensity (P-I) function. Two-way (list No. and Intensity) repeated measurement analysis of variance and Post-Hoc Tukey HSD test indicated that 22 lists were equivalent. Phase II: Twenty-two oral/aural normal adults were recruited to assess monosyllable recognition scores with the 22 equivalent lists at 10 dB HL(Speech), according to the Latin-Square design. Tests were administered twice for all participants with the same procedure and situation during 6 to 35 day intervals. The differences in scores (after a "rationalized" arcsine transformation) among 22 lists across over the two sessions is 9.3%, the data were collected from 22 participants, the measurement error was calculated by SD (standard deviation), the critical difference (CD) for test score improvement was 18.3% (determined as SD x 1.96, in 95% confidence level). Phase III: Eighteen participants with sensorineural hearing loss were recruited to assess recognition perception using 18 equivalent monosyllable lists at 30 dB suprathreshold based on Latin-Square design. Tests were administered twice by using the same procedure and situation within 1 to 16 day intervals. The same approach in Phase II was utilized to calculate SD (8.3%). The CD was calculated as 16.3% (in 95% confidence level). RESULTS: A set of standardized Mandarin recognition assessment material had been developed and it consisted of 22 equivalent phonemic-balanced lists with 25 monosyllables each. Approximately, every single list took 2 minutes, and thus it might be appropriate for clinical assessment. The P-I functions reveal that the recognition threshold was (8.30 +/- 0.84) dB HL(speech) and the slope of PI functions was (4.0 +/- 0.3)%/dB for adults with normal hearing. When a set of Mandarin monosyllable lists was utilized as an assessment tool, the critical difference of 18.3% (for normal-hearing adults) and 16.3% (for hearing-impaired adults) would be a key for clinicians to assess the improvement of speech recognition ability appropriately with statistically significance. CONCLUSION: In this study, a new Mandarin monosyllabic lists has been successfully developed with a sufficient validity, reliability and sensitivity for clinical evaluations, thus it might be convenience and helpful to be used as a standardized speech recognition assessment tool in China.

[Audiological and vestibular evaluation of new coagulation factor C homology mutation carriers in a Chinese family].

OBJECTIVE: To analyze the clinical features of audiological and vestibular function in a Chinese family with late onset autosomal dominant nonsyndromic sensorineural hearing loss. METHODS: Comprehensive audiological and vestibular evaluation including pure tone audiometry, auditory brainstem response (ABR), electrocochleogram (EcochG), oculomotor testing, caloric tests, rotational testing, computerized dynamic posturography and vestibular evoked myogenic potentials (VEMP) were conducted to identify the hearing and vestibular impairment. RESULTS: All affected family members shared sensorineural hearing loss with full penetrance starting between the second and fifth decade of life as a high frequency loss which progresses to a severe to profound loss at the sixth to seventh decade. The extensive vestibular evaluation indicated that all affected members performed normally in computerized dynamic posturography and caloric testing. Impairment of the saccular otolith in all of six affected members was suggested by results of the VEMP test. The velocity step test generated abnormal time constants and sinusoidal oscillation test generated abnormal gains and phase in affected members indicated that horizontal canal vestibular hyporeflexia in history. All affected subjects examined in this family showed completely normal ocular motor responses in oculomotor testing, including smooth pursuit, optokinetic nystagmus, gaze and saccade. CONCLUSIONS: The predominant feature of the Chinese DFNA9 family was that all the affected subjects harboring COCH mutation in the vWFA2 domain didn't suffer the vestibular symptoms during their life time and comprehensive vestibular assessment revealed only subtle vestibular hypofunction in affected members of this family. There is a genotype-phenotype correlation in DFNA9.